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List of methylphenidate analogues

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3D molecular rendering ofmethylphenidate (MPH)

This is a list ofmethylphenidate (MPH or MPD)analogues, orPhenidates. The most well known compound from this family, methylphenidate, is widely prescribed around the world for the treatment ofattention deficit hyperactivity disorder (ADHD) and certain other indications. Several other derivatives includingrimiterol,phacetoperane andpipradrol also have more limited medical application. A rather larger number of these compounds have been sold in recent years asdesigner drugs, either as quasi-legal substitutes for illicit stimulants such asmethamphetamine orcocaine, or as purported "study drugs" ornootropics.^[1]^[2]^[3]

More structurally diverse compounds such asdesoxypipradrol (and thuspipradrol, including such derivatives asAL-1095,diphemethoxidine,SCH-5472 andD2PM), and evenmefloquine,2-benzylpiperidine,rimiterol,enpiroline andDMBMPP, can also be considered structurally related, with the former ones also functionally so, as loosely analogous compounds. Theacyl group has sometimes been replaced with similar lengthketones to increase duration. Alternatively, the methoxycarbonyl has in some cases been replaced with analkyl group.^[4]^[5]

Dozens more phenidates and related compounds are known from the academic and patent literature, andmolecular modelling andreceptor binding studies have established that the aryl and acyl substituents in the phenidate series are functionally identical to the aryl and acyl groups in thephenyltropane series of drugs, suggesting that the central core of these molecules is primarily acting merely as a scaffold to correctly orientate the binding groups, and for each of thehundreds of phenyltropanes that are known, there may be a phenidate equivalent with a comparable activity profile. Albeit with the respective difference in their entropy of binding: cocaine being −5.6 kcal/mol and methylphenidate being −25.5 kcal/mol (Δ s°, measured using [³H]GBR 1278 @ 25 °C).^[a]

Notable phenidate derivatives

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General structure of phenidate derivatives, where R is nearly always hydrogen but can be alkyl, R₁ is usually phenyl or substituted phenyl but rarely otheraryl groups, R₂ is usuallyacyl but can be alkyl or other substitutions, and Cyc is nearly always piperidine but rarely other heterocycles

Common name	Chemical name	CAS #	R₁	R₂
2-BZPD	2-Benzylpiperidine	32838-55-4	phenyl	H
Ritalinic acid	Phenyl(piperidin-2-yl)acetic acid	19395-41-6	phenyl	COOH
Ritalinamide	2-Phenyl-2-(piperidin-2-yl)acetamide	19395-39-2	phenyl	CONH₂
Methylphenidate (MPH)	Methyl phenyl(piperidin-2-yl)acetate	113-45-1	phenyl	COOMe
Phacetoperane (Lidépran)	[(R)-phenyl-[(2R)-piperidin-2-yl]methyl] acetate	24558-01-8	phenyl	OCOMe
Rimiterol	4-{(S)-hydroxy[(2R)-piperidin-2-yl]methyl}benzene-1,2-diol	32953-89-2	3,4-dihydroxyphenyl	hydroxy
Ethylphenidate (EPH)	Ethyl phenyl(piperidin-2-yl)acetate	57413-43-1	phenyl	COOEt
Propylphenidate (PPH)	Propyl phenyl(piperidin-2-yl)acetate	1071564-47-0	phenyl	COOnPr
Isopropylphenidate (IPH)	Propan-2-yl 2-phenyl-2-(piperidin-2-yl)acetate	93148-46-0	phenyl	COOiPr
Butylphenidate (BPH)	Butyl phenyl(piperidin-2-yl)acetate		phenyl	COOnBu
3-Chloromethylphenidate (3-Cl-MPH)	Methyl 2-(3-chlorophenyl)-2-(piperidin-2-yl)acetate	191790-73-5	3-chlorophenyl	COOMe
3-Bromomethylphenidate (3-Br-MPH)	Methyl 2-(3-bromophenyl)-2-(piperidin-2-yl)acetate		3-bromophenyl	COOMe
3-Methylmethylphenidate (3-Me-MPH)	Methyl 2-(3-methylphenyl)-2-(piperidin-2-yl)acetate		3-methylphenyl	COOMe
4-Fluoromethylphenidate (4F-MPH)	Methyl 2-(4-fluorophenyl)-2-(piperidin-2-yl)acetate	1354631-33-6	4-fluorophenyl	COOMe
4-Fluoroethylphenidate (4F-EPH)	Ethyl 2-(4-fluorophenyl)-2-(piperidin-2-yl)acetate	2160555-59-7	4-fluorophenyl	COOEt
4-Fluoroisopropylphenidate (4F-IPH)	Propan-2-yl 2-(4-fluorophenyl)-2-(piperidin-2-yl)acetate		4-fluorophenyl	COOiPr
4-Chloromethylphenidate (4-Cl-MPH)	Methyl 2-(4-chlorophenyl)-2-(piperidin-2-yl)acetate	680996-44-5	4-chlorophenyl	COOMe
3,4-Dichloromethylphenidate (3,4-DCMP)	Methyl 2-(3,4-dichlorophenyl)-2-(piperidin-2-yl)acetate	1400742-68-8	3,4-dichlorophenyl	COOMe
3,4-Dichloroethylphenidate (3,4-DCEP)	Ethyl 2-(3,4-dichlorophenyl)-2-(piperidin-2-yl)acetate		3,4-dichlorophenyl	COOEt
4-Bromomethylphenidate (4-Br-MPH)	Methyl 2-(4-bromophenyl)-2-(piperidin-2-yl)acetate	203056-13-7	4-bromophenyl	COOMe
4-Bromoethylphenidate (4-Br-EPH)	Ethyl 2-(4-bromophenyl)-2-(piperidin-2-yl)acetate	1391486-43-3	4-bromophenyl	COOEt
4-Methylmethylphenidate (4-Me-MPH)	Methyl 2-(4-methylphenyl)-2-(piperidin-2-yl)acetate	191790-79-1	4-methylphenyl	COOMe
4-Methylisopropylphenidate (4-Me-IPH)	Propan-2-yl 2-(4-methylphenyl)-2-(piperidin-2-yl)acetate		4-methylphenyl	COOiPr
4-Nitromethylphenidate (4-NO2-MPH)	Methyl 2-(4-nitrophenyl)-2-(piperidin-2-yl)acetate		4-nitrophenyl	COOMe
Methylenedioxymethylphenidate (MDMPH)	Methyl (1,3-benzodioxol-5-yl)(piperidin-2-yl)acetate		3,4-methylenedioxyphenyl	COOMe
Methylnaphthidate (HDMP-28)	Methyl (naphthalen-2-yl)(piperidin-2-yl)acetate	231299-82-4	naphthalen-2-yl	COOMe
Ethylnaphthidate (HDEP-28)	Ethyl (naphthalen-2-yl)(piperidin-2-yl)acetate	2170529-69-6	naphthalen-2-yl	COOEt
Isopropylnaphthidate	Propan-2-yl (naphthalen-2-yl)(piperidin-2-yl)acetate		naphthalen-2-yl	COOiPr
MTMP	Methyl (thiophen-2-yl)(piperidin-2-yl)acetate		thiophen-2-yl	COOMe
α-acetyl-2-benzylpiperidine	1-Phenyl-1-(piperidin-2-yl)propan-2-one		phenyl	acetyl
CPMBP	2-[1-(3-chlorophenyl)-3-methylbutyl]piperidine		3-chlorophenyl	isobutyl
Desoxypipradrol (2-DPMP)	2-benzhydrylpiperidine	519-74-4	phenyl	phenyl
Pipradrol (Meratran)	Diphenyl(piperidin-2-yl)methanol	467-60-7	phenyl	hydroxy, phenyl

Related compounds

A number of related compounds are known which fit the same general structural pattern, but with substitution on the piperidine ring (e.g.SCH-5472,Difemetorex, N-benzylethylphenidate), or thepiperidine ring replaced by other heterocycles such aspyrrolidine (e.g.diphenylprolinol,2-Diphenylmethylpyrrolidine),morpholine (e.g. Methylmorphenate,3-Benzhydrylmorpholine) orquinoline (e.g.AL-1095,Butyltolylquinuclidine).

Structure	Common name	Chemical name	CAS #
	SCH-5472	2-benzhydryl-1-methyl-piperidin-3-ol	20068-90-0
	Difemetorex	2-[2-(diphenylmethyl)piperidin-1-yl]ethanol	13862-07-2
	CTDP-32476	(2R)-2-[(1R)-1-(4-chlorophenyl)-3-methylbutyl]piperidine	928046-68-8
	N-benzylethylphenidate	Ethyl (1-benzylpiperidin-2-yl)(phenyl)acetate
	Serdexmethylphenidate	(1-((((R)-2-((R)-2-methoxy-2-oxo-1-phenylethyl)piperidine-1-carbonyl)oxy)methyl)pyridin-1-ium-3-carbonyl)-L-serinate chloride	1996626-30-2
	DMBMPP	2-(2,5-dimethoxy-4-bromobenzyl)-6-(2-methoxyphenyl)piperidine	1391499-52-7
	Diphenylprolinol (D2PM)	diphenyl(pyrrolidin-2-yl)methanol	22348-32-9
	2-Benzhydrylpyrrolidine	2-(Diphenylmethyl)pyrrolidine	119237-64-8
	HDMP-29	Methyl (naphthalen-2-yl)(pyrrolidin-2-yl)acetate
	Methylmorphenate	Methyl morpholin-3-yl(phenyl)acetate
	3-Benzhydrylmorpholine	3-(diphenylmethyl)morpholine	93406-27-0
	AL-1095	2-(1-phenyl-1-(p-chlorophenyl)methyl)-3-hydroxyquinuclidine	54549-19-8
	Butyltolylquinuclidine	(2R,3S,4S)-2-butyl-3-p-tolylquinuclidine
^[7]^[8]	2-Benzhydrylpiperazine

Isomerism

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Alternate two dimensional rendering of "D-*threo*-methylphenidate"; demonstrating the plasticity of the piperidine ring in a'flexed' or "chair" conformation. (the latter term can denote a structure containing a bridge in the ring when so-named, unlike the above).

N.B. although thecyclohexane conformation, if considering both the hydrogen on the plain bond and the implicit carbon on the dotted bond are not shown as positioned as would be for the least energy state inherent to what rules apply, internally, to the molecule in and of itself: possibility of movement between putative other ligand sites in suchwise, here regarding what circumstance allows for describing it as "flexed" thus mean it has shown tendency for changein situ depending on its environment and adjacent sites of potential interaction as against its least energy state.

Methylphenidate (and its derivatives) have twochiral centers, meaning that it, and each of its analogues, have four possibleenantiomers, each with differingpharmacokinetics and receptor binding profiles. In practice methylphenidate is most commonly used as pairs ofdiastereomers rather than isolated single enantiomers or a mixture of all four isomers. Forms include the racemate, the enantiopure (dextro or levo) of its stereoisomers;erythro orthreo (either + or -) among its diastereoisomers, thechiral isomers S,S; S,R/R,S or R,R and, lastly, theisomeric conformers (which are not absolute) of either itsanti- orgauche- rotamer. The variant with optimized efficacy is not the usually attested generic or common pharmaceutical brands (e.g. Ritalin,Daytrana etc.) but the (R,R)-dextro-(+)-threo-anti (sold asFocalin), which has a binding profile on par with or better than that ofcocaine.^[b] (Note however the measure of fivefold (5×) discrepancy in the entropy of binding at their presumed shared target binding site, which may account for the higher abuse potential of cocaine over methylphenidate despite affinity for associating;i.e the latter dissociates more readily once bound despite efficacy for binding.^[c]) Furthermore, the energy to change between its two rotamers involves the stabilizing of the hydrogen bond between the protonated amine (of an 8.5pK_a) with the ester carbonyl resulting in reduced instances of "gauche—gauche" interactions via its favoring for activity the "anti"-conformer for putative homergic-psychostimulating pharmacokinetic properties, postulating that one inherent conformational isomer ("anti") is necessitated for the activity of thethreo diastereoisomer.^[d]

Also of note is that methylphenidate indemethylated form is acidic; ametabolite (and precursor) known asritalinic acid.^[10] This gives the potential to yield aconjugate salt^[11] form effectively protonated by a salt nearly chemically duplicate/identical to its own structure; creating a "methylphenidateritalinate".^[12]

Receptor binding profiles of selected methylphenidate analogues

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Aryl substitutions

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Phenyl ring substituted methylphenidate analogues^[e]
S. Singh's alphanumeric assignation (name)	R¹	R²	IC₅₀ (nM) (Inhibition of[³H]WIN 35428 binding)	IC₅₀ (nM) (Inhibition of [³H]DA uptake)	Selectivity uptake/binding

(D-threo-methylphenidate)	H, H		33	244 ± 142 (171 ± 10)	7.4
(L-threo-methylphenidate)	540	5100 (1468 ± 112)	9.4
(D/L-threo-methylphenidate) "eudismic ratio"	6.4	20.9 (8.6)	-
(DL-threo-methylphenidate)	83.0 ± 7.9	224 ± 19	2.7
(R-benzoyl-methylecgonine) (cocaine)	(H, H)		173 ± 13	404 ± 26	2.3

351a (4F-MPH)	F	H y d r o g e n i.e. H	35.0 ± 3.0	142 ± 2.0	4.1
351b	Cl		20.6 ± 3.4	73.8 ± 8.1	3.6
351c	Br		6.9 ± 0.1	26.3 ± 5.8	3.8
351d	(d) Br		-	22.5 ± 2.1	-
351e	(l) Br		-	408 ± 17	-
351d/e "eudismic ratio"	(d/l) Br		-	18.1	-
351f	I		14.0 ± 0.1	64.5 ± 3.5	4.6
351g	OH		98.0 ± 10	340 ± 70	3.5
351h	OCH₃		83 ± 11	293 ± 48	3.5
351i	(d) OCH₃		-	205 ± 10	-
351j	(l) OCH₃		-	3588 ± 310	-
351i/j "eudismic ratio"	(d/l) OCH₃		-	17.5	-
351k (4-Me-MPH)	CH₃		33.0 ± 1.2	126 ± 1	3.8
351l	t-Bu		13500 ± 450	9350 ± 950	0.7
351m	NH₂.HCl		34.6 ± 4.0	115 ± 10	3.3
351n	NO₂		494 ± 33	1610 ± 210	3.3

352a	F		40.5 ± 4.5	160 ± 0.00	4.0
352b	Cl		5.1 ± 1.6	23.0 ± 3.0	4.5
352c	Br		4.2 ± 0.2	12.8 ± 0.20	3.1
352d	OH		321 ± 1.0	790 ± 30	2.5
352e	OMe		288 ± 53	635 ± 35	0.2
352f	Me		21.4 ± 1.1	100 ± 18	4.7
352g	NH₂.HCl		265 ± 5	578 ± 160	2.2
353a	2′-F		1420 ± 120	2900 ± 300	2.1
353b	2′-Cl		1950 ± 230	2660 ± 140	1.4
353c	2′-Br		1870 ± 135	3410 ± 290	1.8
353d	2′-OH		23100 ± 50	35,800 ± 800	1.6
353e	2′-OCH₃		101,000 ± 10,000	81,000 ± 2000	0.8
354a (3,4-DCMP)	Cl, Cl (3′,4′-Cl₂)		5.3 ± 0.7	7.0 ± 0.6	1.3
354b	I	OH	42 ± 21	195 ± 197	4.6
354c	OMe, OMe (3′,4′-OMe₂)		810 ± 10	1760 ± 160	2.2

Both analogues374 &375 displayed higher potency than methylphenidate at DAT. In further comparison,375 (the 2-naphthyl) was additionally two & a half times more potent than374 (the 1-naphthyl isomer).^[f]

Aryl exchanged analogues

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Phenyl ring modified methylphenidate analogues^[g]
S. Singh's alphanumeric assignation (name)	Ring	K_i (nM) (Inhibition of [¹²⁵I]IPT binding)	K_i (nM) (Inhibition of [³H]DA uptake)	Selectivity uptake/binding
(D-threo-methylphenidate)	benzene	324	-	-
(DL-threo-methylphenidate)	benzene	82 ± 77	429 ± 88	0.7
374	1-naphthalene	194 ± 15	1981 ± 443	10.2
375 (HDMP-28)	2-naphthalene	79.5	85.2 ± 25	1.0
376	benzyl	>5000	-	-

HDMP-29, a manifold (multiple augmented) analogue of both the phenyl (to a 2-naphthalene) and piperidine (to a 2-pyrrolidine) rings.^[13]

Piperidine nitrogen methylated phenyl-substituted variants

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N-methyl phenyl ring substituted methylphenidate analogues^[h]
S. Singh's alphanumeric assignation (name)	R	IC₅₀ (nM) (Inhibition of binding at DAT)

373a	H	500 ± 25
373b	4″-OH	1220 ± 140
373c	4″-CH₃	139 ± 13
373d	3″-Cl	161 ± 18
373e	3″-Me	108 ± 16

Cycloalkane extensions, contractions & modified derivatives

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Piperidine ring modified methylphenidate analogues^[i]
S. Singh's alphanumeric assignation (name)	Cycloalkane ring	K_i (nM) (Inhibition of binding)
380	2-pyrrolidine (cyclopentane)	1336 ± 108
381	2-azepane (cycloheptane)	1765 ± 113
382	2-azocane (cyclooctane)	3321 ± 551
383	4-1,3-oxazinane (cyclohexane)	6689 ± 1348

Methyl 2-(1,2-oxazinan-3-yl)-2-phenylacetate

Methyl 2-(1,3-oxazinan-2-yl)-2-phenylacetate

The two other (in addition to compound383) potential oxazinane methylphenidate analogues.

Methyl 2-phenyl-2-(morpholin-3-yl)acetate
A.K.A.Methyl 2-morpholin-3-yl-2-phenylacetate

☜Methylmorphenate methylphenidate analogue.^[14]

Azido-iodo-N-benzyl analogues

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Structures of Azido-iodo-N-benzyl analogues of methylphenidate with affinities.^[15]

Azido-iodo-N-benzyl methylphenidate analogs inhibitition of [³H]WIN 35428 binding and [³H]dopamine uptake at hDAT N2A neuroblastoma cells.^[15]
(EachK_i or IC₅₀ value represents data from at least three independent experiments with each data point on the curve performed in duplicate)
Compound	R¹	R²	K_i (nM) (Inhibition of [³H]WIN 35428 binding)	IC₅₀ (nM) (Inhibition of [³H]DA uptake)
(±)—threo-methylphenidate	H	H	25 ± 1	156 ± 58
(±)—4-I-methylphenidate	para-iodo	H	14 ± 3^ɑ	11 ± 2^b
(±)—3-I-methylphenidate	meta-iodo	H	4.5 ± 1^ɑ	14 ± 5^b

(±)—p-N₃-N-Bn-4-I-methylphenidate	para-iodo	para-N₃-N-Benzyl	363 ± 28^ɑ	2764 ± 196^bc
(±)—m-N₃-N-Bn-4-I-methylphenidate	para-iodo	meta-N₃-N-Benzyl	2754 ± 169^ɑ	7966 ± 348^bc
(±)—o-N₃-N-Bn-4-I-methylphenidate	para-iodo	ortho-N₃-N-Benzyl	517 ± 65^ɑ	1232 ± 70^bc
(±)—p-N₃-N-Bn-3-I-methylphenidate	meta-iodo	para-N₃-N-Benzyl	658 ± 70^ɑ	1828 ± 261^bc
(±)—m-N₃-N-Bn-3-I-methylphenidate	meta-iodo	meta-N₃-N-Benzyl	2056 ± 73^ɑ	4627 ± 238^bc
(±)—o-N₃-N-Bn-3-I-methylphenidate	meta-iodo	ortho-N₃-N-Benzyl	1112 ± 163^ɑ	2696 ± 178^bc
(±)—N-Bn-methylphenidate	H	N-Benzyl	—	—
(±)—N-Bn-3-chloro-methylphenidate	3-Cl	N-Benzyl	—	—
(±)—N-Bn-3,4-dichloro-methylphenidate	3,4-diCl	N-Benzyl	—	—
(±)—p-chloro-N-Bn-methylphenidate	H	para-Cl-N-Benzyl	—	—
(±)—p-methoxy-N-Bn-methylphenidate	H	para-OMe-N-Benzyl	—	—
(±)—m-chloro-N-Bn-methylphenidate	H	meta-Cl-N-Benzyl	—	—
(±)—p-nitro-N-Bn-methylphenidate	H	para-NO₂-N-Benzyl	—	—

^ɑp <0.05 versusK_i of (±)—threo-methylphenidate.
^bp <0.05 versus IC₅₀ of (±)—threo-methylphenidate.
^cp <0.05 versus its correspondingK_i.

Additional arene/nitrogen-linked MPH analogs

ChEMBL1254008^[16]

ChEMBL1255099^[17]

Alkyl substituted-carbomethoxy analogues

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AlkylRR/SS diastereomer analogs of methylphenidate^[4]
(*RS/SR* diastereomer values of otherwise same compounds given in small grey typeface^[4])
Structure	R¹	R²	R³	Dopamine transporterK_i (nM) (Inhibition of [I¹²⁵H]RTI-55 binding)	DA uptake IC₅₀ (nM)	Serotonin transporterK_i (nM) (Inhibition of [I¹²⁵H]RTI-55 binding)	5HT uptake IC₅₀ (nM)	Norepinephrine transporterK_i (nM) (Inhibition of [I¹²⁵H]RTI-55 binding)	NE uptake IC₅₀ (nM)	NE/DA selectivity (binding displacement)	NE/DA selectivity (uptake blocking)
Cocaine	— ^ɑ	—^b	—^c	500 ± 65	240 ± 15	340 ± 40	250 ± 40	500 ± 90	210 ± 30	1.0	0.88

	H	COOCH₃	H	110 ± 9	79 ± 16	65,000 ± 4,000	5,100 ± 7,000	660 ± 50	61 ± 14	6.0	0.77
	4-chloro	COOCH₃	H	25 ± 8 2,000 ± 600	11 ± 28 2,700 ± 1,000	6,000 ± 100 5,900 ± 200	>9,800 >10 mM	110 ± 40 >6,100	11 ± 3 1,400 ± 400	4.4	1.0
	4-chloro	methyl	H	180 ± 70 >3,900	22 ± 7 1,500 ± 700	4,900 ± 500 >9,100	1,900 ± 300 4,700 ± 800	360 ± 140 >6,300	35 ± 13 3,200 ± 800	2.0	1.6
	4-chloro	ethyl	H	37 ± 10 1,800 ± 300	23 ± 5 2,800 ± 700	7,800 ± 800 4,200 ± 400	2,400 ± 400 4,100 ± 1,000	360 ± 60 >9,200	210 ± 30 1,300 ± 400	9.7	9.1
	4-chloro	propyl	H	11 ± 3 380 ± 40	7.4 ± 0.4 450 ± 60	2,700 ± 600 3,200 ± 1,100	2,900 ± 1,100 1,300 ± 7	200 ± 80 1,400 ± 400	50 ± 15 200 ± 50	18.0	6.8
	4-chloro	isopropyl	H	46 ± 16 900 ± 320	32 ± 6 990 ± 280	5,300 ± 1,300 >10 mM	3,300 ± 400 —	810 ± 170 >10 mM	51 ± 20 —	18.0	1.6
	4-chloro	butyl	H	7.8 ± 1.1 290 ± 70	8.2 ± 2.1 170 ± 40	4,300 ± 400 4,800 ± 700	4,000 ± 400 3,300 ± 600	230 ± 30 1,600 ± 300	26 ± 7 180 ± 60	29.0	3.2
	4-chloro	isobutyl	H	16 ± 4 170 ± 50	8.6 ± 2.9 380 ± 130	5,900 ± 900 4,300 ± 500	490 ± 80 540 ± 150	840 ± 130 4,500 ± 1,500	120 ± 40 750 ± 170	53.0	14.0
	4-chloro	pentyl	H	23 ± 7 870 ± 140	45 ± 14 650 ± 20	2,200 ± 100 3,600 ± 1,000	1,500 ± 300 1,700 ± 700	160 ± 40 1,500 ± 300	49 ± 16 860 ± 330	7.0	1.1
	4-chloro	isopentyl	H	3.6 ± 1.2 510 ± 170	14 ± 2 680 ± 120	5,000 ± 470 6,700 ± 500	7,300 ± 1,400 >8,300	830 ± 110 12,000 ± 1,400	210 ± 40 3,000 ± 540	230.0	15.0
	4-chloro	neopentyl	H	120 ± 40 600 ± 40	60 ± 2 670 ± 260	3,900 ± 500 3,500 ± 1,000	>8,300 1,800 ± 600	1,400 ± 400 >5,500	520 ± 110 730 ± 250	12.0	8.7
	4-chloro	cyclopentylmethyl	H	9.4 ± 1.5 310 ± 80	21 ± 1 180 ± 20	2,900 ± 80 3,200 ± 700	2,100 ± 900 5,600 ± 1,400	1,700 ± 600 2,600 ± 800	310 ± 40 730 ± 230	180.0	15.0
	4-chloro	cyclohexylmethyl	H	130 ± 40 260 ± 30	230 ± 70 410 ± 60	900 ± 400 3,700 ± 500	1,000 ± 200 6,400 ± 1,300	4,200 ± 200 4,300 ± 200	940 ± 140 1,700 ± 600	32.0	4.1
	4-chloro	benzyl	H	440 ± 110 550 ± 60	370 ± 90 390 ± 60	1,100 ± 200 4,300 ± 800	1,100 ± 200 4,700 ± 500	2,900 ± 800 4,000 ± 800	2,900 ± 600 >8,800	6.6	7.8
	4-chloro	phenethyl	H	24 ± 9 700 ± 90	160 ± 20 420 ± 140	640 ± 60 1,800 ± 70	650 ± 210 210 ± 900^d	1,800 ± 600 2,400 ± 700	680 ± 240 610 ± 150	75.0	4.3
	4-chloro	phenpropyl	H	440 ± 150 2,900 ± 900	290 ± 90 1,400 ± 400	700 ± 200 1,500 ± 200	1,600 ± 300 1,200 ± 400	490 ± 100 1,500 ± 200	600 ± 140 1,700 ± 200	1.1	2.1
	4-chloro	3-pentyl	H	400 ± 80 >5,700	240 ± 60 1,200 ± 90	3,900 ± 300 4,800 ± 1,100	>9,400 >9,600	970 ± 290 4,300 ± 200	330 ± 80 3,800 ± 30	2.4	1.4
	4-chloro	cyclopentyl	H	36 ± 10 690 ± 140	27 ± 8.3 240 ± 30	5,700 ± 1,100 4,600 ± 700	4,600 ± 800 4,200 ± 900	380 ± 120 3,300 ± 800	44 ± 18 1,000 ± 300	11.0	1.6
	3-chloro	isobutyl	H	3.7 ± 1.1 140 ± 30	2.8 ± 0.4 88 ± 12	3,200 ± 400 3,200 ± 400	2,100 ± 100 870 ± 230	23 ± 6 340 ± 50	14 ± 1 73 ± 5	6.2	5.0
	3,4-dichloro	COOCH₃	H	1.4 ± 0.1 90 ± 14	23 ± 3 800 ± 110	1,600 ± 150 2,500 ± 420	540 ± 110 1,100 ± 90	14 ± 6 4,200 ± 1,900	10 ± 1 190 ± 50	10.0	0.43
	3,4-dichloro	propyl	H	0.97 ± 0.31 43 ± 9	4.5 ± 0.4 88 ± 32	1,800 ± 500 450 ± 80	560 ± 120 180 ± 60	3.9 ± 1.4 30 ± 8	8.1 ± 3.8 47 ± 22	4.0	1.8
	3,4-dichloro	butyl	H	2.3 ± 0.2 29 ± 5	5.7 ± 0.5 67 ± 13	1,300 ± 300 1,100 ± 200	1,400 ± 300 550 ± 80	12 ± 3 31 ± 11	27 ± 10 63 ± 27	5.2	4.7
	3,4-dichloro	isobutyl	H	1.0 ± 0.5 31 ± 11	5.5 ± 1.3 13 ± 3	1,600 ± 100 450 ± 40	1,100 ± 300 290 ± 60	25 ± 9 120 ± 30	9.0 ± 1.2 19 ± 3	25.0	1.6
	3,4-dichloro	isobutyl	CH₃	6.6 ± 0.9 44 ± 12	13 ± 4 45 ± 4	1,300 ± 200 1,500 ± 300	1,400 ± 500 2,400 ± 700	190 ± 60 660 ± 130	28 ± 3 100 ± 19	29.0	2.2
	4-methoxy	isobutyl	H	52 ± 16 770 ± 220	25 ± 9 400 ± 120	2,800 ± 600 950 ± 190	3,500 ± 500 1,200 ± 300	3,100 ± 200 16,000 ± 2,000	410 ± 90 1,600 ± 400	60.0	16.0
	3-methoxy	isobutyl	H	22 ± 5 950 ± 190	35 ± 12 140 ± 20	4,200 ± 400 3,800 ± 600	2,700 ± 800 2,600 ± 300	3,800 ± 500 12,000 ± 2,300	330 ± 40 1,400 ± 90	170.0	9.4
	4-isopropyl	isobutyl	H	3,300 ± 600 >6,500	4,000 ± 400 >9,100	3,300 ± 600 1,700 ± 500	4,700 ± 700 1,700 ± 100	2,500 ± 600 3,200 ± 600	7,100 ± 1,800 >8,700	0.76	1.8
	H	COCH₃	H	370 ± 70	190 ± 50	7,800 ± 1,200	>9,700	2,700 ± 400	220 ± 30	7.3	1.2

^ɑ H = Equivalent overlay of structure sharing functional group
^b CO₂CH₃ (i.e. COOCH₃) = Equivalent overlay of structure sharing functional group
^c CH₃ = Equivalent overlay of structure sharing functional group
^d possible typographical error in original source;e.g. 2,100 ± 900 or 900 ± 210

Restricted rotational analogs of methylphenidate (quinolizidines)

[edit]

Two of the compounds tested, the weakest two @ DAT & second to the final two on the table below, were designed to elucidate the necessity of both constrained rings in the efficacy of the below series of compounds at binding by removing one or the other of the two rings in their entirety. The first of the two retain the original piperidine ring had with methylphenidate but has the constrained B ring that is common to the restricted rotational analogues thereof removed. The one below lacks the piperdine ring native to methylphenidate but keeps the ring that hindered the flexibility of the original MPH conformation. Though their potency at binding is weak in comparison to the series, with the potency shared being approximately equal between the two; the latter compound (the one more nearly resembling the substrate class of dopaminergic releasing agents similar tophenmetrazine) is 8.3-fold more potent @ DA uptake.

Binding assays^g of rigid methylphenidate analogues^[18]
Compound^ɑ	R & X substitution(s)	K_i (nM) @ DAT with [³3]WIN 35,065-2	n_H @ DAT with [³3]WIN 35,065-2	K_i (nM) or % inhibition @ NET with [³3]Nisoxetine	n_H @ NET with [³3]Nisoxetine	K_i (nM) or % inhibition @ 5-HTT with [³3]Citalopram	n_H @ 5-HTT with [³3]Citalopram	[³3]DA uptake IC₅₀ (nM)	Selectivity [³3]Citalopram / [³3]WIN 35,065-2	Selectivity [³3]Nisoxetine / [³3]WIN 35,065-2	Selectivity [³3]Citalopram / [³3]Nisoxetine
Cocaine	—	156 ± 11	1.03 ± 0.01	1,930 ± 360	0.82 ± 0.05	306 ± 13	1.12 ± 0.15	404 ± 26	2.0	12	0.16
Methylphenidate	—	74.6 ± 7.4	0.96 ± 0.08	270 ± 23	0.76 ± 0.06	14 ± 8%^f	—	230 ± 16	>130	3.6	>47
3′,4′-dichloro-MPH	—	4.76 ± 0.62	2.07 ± 0.05	ND^h	—	667 ± 83	1.07 ± 0.04	7.00 ± 140	140	—	—

	—	6,610 ± 440	0.91 ± 0.01	11%^b	—	3,550 ± 70	1.79 ± 0.55	8,490 ± 1,800	0.54	>0.76	<0.7

	H	76.2 ± 3.4	1.05 ± 0.05	138 ± 9.0	1.12 ± 0.20	5,140 ± 670	1.29 ± 0.40	244 ± 2.5	67	1.8	37
	3′,4′-diCl	3.39 ± 0.77	1.25 ± 0.29	28.4 ± 2.5	1.56 ± 0.80	121 ± 17	1.16 ± 0.31	11.0 ± 0.00	36	8.4	4.3
	2′-Cl	480 ± 46	1.00 ± 0.09	2,750; 58%^b	0.96	1,840 ± 70	1.18 ± 0.06	1,260 ± 290	3.8	5.7	0.67

	—	34.6 ± 7.6	0.95 ± 0.18	160 ± 18	1.28 ± 0.12	102 ± 8.2	1.01 ± 0.02	87.6 ± 0.35	3.0	4.6	0.64

	CH₂OH	2,100 ± 697	0.87 ± 0.09	ND^h	—	16.2 ± 0.05%^f	—	10,400 ± 530	>4.8	—	—
	CH₃	7,610 ± 800	1.02 ± 0.03	8.3%^b	—	11 ± 5%^f	—	7,960 ± 290	>1.3	≫0.66	—

	^d R=OCH₃, X=H	570 ± 49	0.94 ± 0.10	2,040; 64 ± 1.7%^f	0.73	14 ± 3%^f	—	1,850 ± 160	>18	3.6	>4.9
	R=OH, X=H	6,250 ± 280	0.86 ± 0.03	23.7 ± 4.1%^b	—	1 ± 1%^f	—	10,700 ± 750	≫1.6	>0.80	—
	R=OH, X=3′,4′-diCl	35.7 ± 3.2	1.00 ± 0.09	367 ± 42	1.74 ± 0.87	2,050 ± 110	1.15 ± 0.12	ND^h	57	10	5.6

	H	908 ± 160	0.88 ± 0.05	4030; 52%^b	1.04	5 ± 1%^f	—	12,400 ± 1,500	≫11	4.4	≫2.5
	3′,4′-diCl	14.0 ± 1.2	1.27 ± 0.20	280 ± 76	0.68 ± 0.09	54 ± 2%^f	—	ND^h	~710	20	~36

	R=OH, X=H	108 ± 7.0	0.89 ± 0.10	351 ± 85	0.94 ± 0.27	12 ± 2%^f	—	680 ± 52	>93	3.3	>28
	R=OH, X=3′,4′-diCl	2.46 ± 0.52	1.39 ± 0.20	27.9 ± 3.5	0.70 ± 0.01	168	1.02	ND^h	68	11	6.0
	R=OCH₃, X=H	10.8 ± 0.8	0.97 ± 0.07	63.7 ± 2.8	0.84 ± 0.04	2,070; 73 ± 5%^f	0.90	61.0 ± 9.3	190	5.9	32

	R₁=CH₃, R₂=H	178 ± 28	1.23 ± 0.09	694 ± 65	0.88 ± 0.13	427	1.39	368	2.4	3.9	0.62
	R₁=H, R₂=CH₃	119 ± 20	1.17 ± 0.12	76.0 ± 12	0.88 ± 0.06	243	1.17	248	2.0	0.64	3.2

	—	175 ± 8.0	1.00 ± 0.04	1,520 ± 120	0.97 ± 0.06	19 ± 4%^f	—	ND^h	>57	8.69	>6.6

	R=CH₂CH₃, X=H	27.6 ± 1.7	1.29 ± 0.05	441 ± 49	1.16 ± 0.19	2,390; 80%^f	1.12	ND^h	87	15	5.8
	R=CH₂CH₃, X=3′,4′-diCl	3.44 ± 0.02	1.90 ± 0.05	102 ± 19	1.27 ± 0.10	286 ± 47	1.30 ± 0.10	ND^h	83	30	2.8

	R=CH₂CH₃, X=H	5.51 ± 0.93	1.15 ± 0.03	60.8 ± 9.6	0.75 ± 0.07	3,550; 86%^f	0.95	ND^h	640	11	58
	R=CH₂CH₃, X=3′,4′-diCl	4.12 ± 0.95	1.57 ± 0.00	98.8 ± 8.7	1.07 ± 0.07	199 ± 17	1.24 ± 0.00	ND^h	48	24	2.0

	—	6,360 ± 1,300	1.00 ± 0.04	36 ± 10%^c	—	22 ± 7%^f	—	8,800 ± 870	>1.6	—	—

	ⁱ —	4,560 ± 1,100	1.10 ± 0.09	534 ± 210^c	0.96 ± 0.08	53 ± 6%^f	—	1,060 ± 115	~2.2	0.12	~19

	R₁=CH₂OH, R₂=H, X=H	406 ± 4	1.07 ± 0.08	ND^h	—	31.0 ± 1.5%^f	—	1,520 ± 15	>25	—	—
	R₁=CH₂OCH₃, R₂=H, X=H	89.9 ± 9.4	0.97 ± 0.04	ND^h	—	47.8 ± 0.7%^f	—	281 ± 19	~110	—	—
	R₁=CH₂OH, R₂=H, X=3′,4′-diCl	3.91 ± 0.49	1.21 ± 0.06	ND^h	—	276; 94.6%^f	0.89	22.5 ± 1.4	71	—	—
	R₁=H, R₂=CO₂CH₃, X=3′,4′-diCl	363 ± 20	1.17 ± 0.41	ND^h	—	2,570 ± 580	1.00 ± 00.1	317 ± 46	7.1	—	—
	R₁=CO₂CH₃, R₂=H, X=2′-Cl	1,740 ± 200	0.98 ± 0.02	ND^h	—	22.2 ± 2.5%^f	—	2,660 ± 140	>5.7	—	—

^ɑ Compounds tested as hydroclhoride (HCl) salts, unless otherwise noted.
^b % inhibition caused by 5μM
^c % inhibition caused by 10μM, as assayed by SRI
^d Tested as free base
^e Assayed by SRI (appropriate correction factor applied.)
^f % inhibition of 10μM compound.
^g Values expressed asx ± SEM of 2—5 replicate tests. (If no SEM shown, value is for ann of 1.)
^h Not determined
ⁱcf.phenmetrazine & derivatives

Various MPHcongener affinity values inclusive of norepinephrine & serotonin

[edit]

Values fordl-threo-methylphenidate derivatives are themean (s.d.)^[19] of 3—6 determinations, or are the mean of duplicate determinations. Values of other compounds are the mean—s.d. for 3—4 determinations where indicated, or are results of single experiments which agree with the literature. All binding experiments were done in triplicate.^[20]

Binding and uptake IC₅₀ (nM) values for MAT.
Compound	DA	DA Uptake	NE	5HT
Methylphenidate	84 ± 33	153 ± 92	514 ± 74	>50,000
o-Bromomethylphenidate	880 ± 316	—	20,000	—
m-Bromomethylphenidate	4 ± 1	18 ± 11	20 ± 6	3,800
p-Bromomethylphenidate	21 ± 3	45 ± 19	31 ± 7	2,600
p-Hydroxymethylphenidate	125	263 ± 74	270 ± 69	17,000
p-Methyloxymethylphenidate	42 ± 24	490 ± 270	410	11,000
p-Nitromethylphenidate	180	—	360	5,900
p-Iodomethylphenidate	26 ± 14	—	32	1,800^ɑ
m-Iodo-p-hydroxymethylphenidate	42 ± 21	195 ± 197	370 ± 64	5,900
N-Methylmethylphenidate	1,400	—	2,800	40,000
d-threo-Methylphenidate	33	—	244 ± 142	>50,000
l-threo-Methylphenidate	540	—	5,100	>50,000
dl-erythro-o-Bromomethylphenidate	10,000	—	50,000	—
Cocaine	120	313 ± 160	2,100	190
WIN 35,428	13	—	530	72
Nomifensine	29 ± 16	—	15 ± 2	1,300^ɑ
Mazindol	9 ± 5	—	3 ± 2	92
Desipramine	1,400	—	3.5	200
Fluoxetine	3,300	—	3,400	2.4

^ɑ Denotes that preparation of membrane and results extrapolated therefrom originated from frozen tissue, which is known to change results when interpreting against fresh tissue experiments.

p-hydroxymethylphenidate displays low brain penetrability, ascribed to its phenolic hydroxyl group undergoing ionization at physiologicalpH.

References

[edit]

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^Kim DI, Deutsch HM, Ye X, Schweri MM (May 2007). "Synthesis and pharmacology of site-specific cocaine abuse treatment agents: restricted rotation analogues of methylphenidate".Journal of Medicinal Chemistry.50 (11):2718–31.doi:10.1021/jm061354p.PMID 17489581.
^Jaykaran (October 2010).""Mean ± SEM" or "Mean (SD)"?".Indian Journal of Pharmacology.42 (5): 329.doi:10.4103/0253-7613.70402.PMC 2959222.PMID 21206631.
^Gatley SJ, Pan D, Chen R, Chaturvedi G, Ding YS (1996). "Affinities of methylphenidate derivatives for dopamine, norepinephrine and serotonin transporters".Life Sciences.58 (12):231–9.doi:10.1016/0024-3205(96)00052-5.PMID 8786705.

Notes

[edit]

^^[6] ←Page #1,006 (82nd page of article) 2nd row, 1st ¶ (orig. ref.: Bonnet, J.-J.; Benmansour, S.; Costenin, J.; Parker, E. M.;Cubeddu, L. X.J. Pharmacol. Exp. Ther.1990,253, 1206)
^^[9] ←Page #1,005 (81st page of article) §VI. Final ¶.
^^[9] ←Page #1,006 (82nd page of article) 2nd column, end of first ¶.
^^[9] ←Page #1,005 (81st page of article) Final § (§VI.) & page #1,006 (82nd page of article) left (1st) column, first ¶ and figure 51.
^^[9] ←Page #1,010 (86th page of article) Table 47, Page #1,007 (83rd page of article) Figure 52
^^[9] ←Page #1,010 (86th page of article) 2nd ¶, lines 2, 3 & 5.
^^[9] ←Page #1,010 (86th page of article) Table 49, Page #1,007 (83rd page of article) Figure 54
^^[9] ←Page #1,010 (86th page of article) Table 48, Page #1,007 (83rd page of article) Figure 53
^^[9] ←Page #1,011 (87th page of article) Table 50, Page #1,007 (83rd page of article) Figure 55

Gatley SJ, Pan D, Chen R, Chaturvedi G, Ding YS (1996). "Affinities of methylphenidate derivatives for dopamine, norepinephrine and serotonin transporters".Life Sciences.58 (12):231–9.doi:10.1016/0024-3205(96)00052-5.PMID 8786705.
Lapinsky DJ, Velagaleti R, Yarravarapu N, Liu Y, Huang Y, Surratt CK, et al. (January 2011)."Azido-iodo-N-benzyl derivatives of threo-methylphenidate (Ritalin, Concerta): Rational design, synthesis, pharmacological evaluation, and dopamine transporter photoaffinity labeling".Bioorganic & Medicinal Chemistry.19 (1):504–12.doi:10.1016/j.bmc.2010.11.002.PMC 3023924.PMID 21129986.
Froimowitz M, Gu Y, Dakin LA, Nagafuji PM, Kelley CJ, Parrish D, et al. (January 2007). "Slow-onset, long-duration, alkyl analogues of methylphenidate with enhanced selectivity for the dopamine transporter".Journal of Medicinal Chemistry.50 (2):219–32.doi:10.1021/jm0608614.PMID 17228864.
Davies HM, Hopper DW, Hansen T, Liu Q, Childers SR (April 2004). "Synthesis of methylphenidate analogues and their binding affinities at dopamine and serotonin transport sites".Bioorganic & Medicinal Chemistry Letters.14 (7):1799–802.doi:10.1016/j.bmcl.2003.12.097.PMID 15026075.
Froimowitz M, Gu Y, Dakin LA, Kelley CJ, Parrish D, Deschamps JR (June 2005). "Vinylogous amide analogs of methylphenidate".Bioorganic & Medicinal Chemistry Letters.15 (12):3044–7.doi:10.1016/j.bmcl.2005.04.034.PMID 15908207.
Schweri MM, Deutsch HM, Massey AT, Holtzman SG (May 2002). "Biochemical and behavioral characterization of novel methylphenidate analogs".The Journal of Pharmacology and Experimental Therapeutics.301 (2):527–35.doi:10.1124/jpet.301.2.527.PMID 11961053.S2CID 314970.
Volz TJ, Bjorklund NL, Schenk JO (September 2005). "Methylphenidate analogs with behavioral differences interact differently with arginine residues on the dopamine transporter in rat striatum".Synapse.57 (3):175–8.doi:10.1002/syn.20161.PMID 15945061.S2CID 24352613.
Lapinsky DJ, Yarravarapu N, Nolan TL, Surratt CK, Lever JR, Tomlinson M, et al. (May 2012)."Evolution of a Compact Photoprobe for the Dopamine Transporter Based on (±)-threo-Methylphenidate".ACS Medicinal Chemistry Letters.3 (5):378–382.doi:10.1021/ml3000098.PMC 3469269.PMID 23066448.
Deutsch HM, Ye X, Shi Q, Liu Z, Schweri MM (April 2001). "Synthesis and pharmacology of site specific cocaine abuse treatment agents: a new synthetic methodology for methylphenidate analogs based on the Blaise reaction".European Journal of Medicinal Chemistry.36 (4):303–11.doi:10.1016/s0223-5234(01)01230-2.PMID 11461755.

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Eugeroics	Adrafinil Armodafinil CRL-40,940 CRL-40,941 Fluorenol Modafinil
Oxazolines	4-Methylaminorex Aminorex Clominorex Cyclazodone Fenozolone Fluminorex Pemoline Thozalinone
Phenethylamines	1-(4-Methylphenyl)-2-aminobutane 1-Methylamino-1-(3,4-methylenedioxyphenyl)propane 2-Fluoroamphetamine 2-Fluoromethamphetamine 2-OH-PEA 2-Phenyl-3-aminobutane 2,3-MDA 3-Fluoroamphetamine 3-Fluoroethamphetamine 3-Methoxyamphetamine 3-Methylamphetamine 4-Fluoroamphetamine 4-Fluoromethamphetamine 4-MA 4-MMA 4-MTA 6-FNE AL-1095 Alfetamine a-Ethylphenethylamine Amfecloral Amfepentorex Amidephrine 2-Amino-1,2-dihydronaphthalene 2-Aminoindane 5-(2-Aminopropyl)indole 2-Aminotetralin Acridorex Amphetamine (Dextroamphetamine,Levoamphetamine) Amphetaminil Arbutamine β-Methylphenethylamine β-Phenylmethamphetamine Benfluorex Benzphetamine BDB BOH 3-Benzhydrylmorpholine BPAP Camfetamine Cathine Chlorphentermine Cilobamine Cinnamedrine Clenbuterol Clobenzorex Cloforex Clortermine Cypenamine D-Deprenyl Denopamine Dimethoxyamphetamine Dimethylamphetamine Dobutamine DOPA (Dextrodopa,Levodopa) Dopamine Dopexamine Droxidopa EBDB Ephedrine Epinephrine Epinine Etafedrine Ethylnorepinephrine Etilamfetamine Etilefrine Famprofazone Fencamfamin Fencamine Fenethylline Fenfluramine (Dexfenfluramine,Levofenfluramine) Fenproporex Feprosidnine Fludorex Formetorex Furfenorex Gepefrine Hexapradol HMMA Hordenine 4-Hydroxyamphetamine 5-Iodo-2-aminoindane Ibopamine Indanylamphetamine Iofetamine Isoetarine Isoprenaline L-Deprenyl (Selegiline) Lefetamine Lisdexamfetamine Lophophine MBDB MDA (tenamfetamine) MDBU MDEA MDMA (midomafetamine) MDMPEA MDOH MDPR MDPEA Mefenorex Mephentermine Metanephrine Metaraminol Mesocarb Methamphetamine (Dextromethamphetamine,Levomethamphetamine) Methoxamine Methoxyphenamine MMA Methoxyphenamine MMDA MMDMA MMMA Morforex N,alpha-Diethylphenylethylamine N,N-Dimethylphenethylamine Naphthylamphetamine Nisoxetine Norepinephrine Norfenefrine Norfenfluramine Normetanephrine L-Norpseudoephedrine Octopamine Orciprenaline Ortetamine Oxifentorex Oxilofrine PBA PCA PCMA PHA Pentorex Phenatine Phenpromethamine Phentermine Phenylalanine Phenylephrine Phenylpropanolamine Pholedrine PIA PMA PMEA PMMA PPAP Prenylamine Propylamphetamine Pseudoephedrine Ropinirole Salbutamol (Levosalbutamol) Sibutramine Solriamfetol Synephrine Theodrenaline Tiflorex Tranylcypromine Tyramine Tyrosine Xylopropamine Zylofuramine
Phenylmorpholines	3-Fluorophenmetrazine Fenbutrazate Fenmetramide G-130 Manifaxine Morazone Morforex Oxaflozane PD-128,907 Phendimetrazine Phenmetrazine 2-Phenyl-3,6-dimethylmorpholine Pseudophenmetrazine Radafaxine
Piperazines	2C-B-BZP 3C-PEP BZP CM156 DBL-583 GBR-12783 GBR-12935 GBR-13069 GBR-13098 GBR-13119 JJC8-088 MeOPP MBZP oMPP Vanoxerine
Piperidines	1-Benzyl-4-(2-(diphenylmethoxy)ethyl)piperidine 2-Benzylpiperidine 2-Methyl-3-phenylpiperidine 3,4-Dichloromethylphenidate 4-Benzylpiperidine 4-Fluoromethylphenidate 4-Methylmethylphenidate Desoxypipradrol Difemetorex Diphenylpyraline Ethylnaphthidate Ethylphenidate Methylnaphthidate Isopropylphenidate JZ-IV-10 Methylphenidate (Dexmethylphenidate) Nocaine Phacetoperane Pipradrol Propylphenidate Serdexmethylphenidate SCH-5472
Pyrrolidines	2-Diphenylmethylpyrrolidine 4-Cl-PVP 5-DBFPV α-PPP α-PBP α-PCYP α-PHiP α-PHP α-PHPP α-PVP α-PVT Diphenylprolinol DMPVP FPOP FPVP MDPPP MDPBP MPBP MPHP MPPP MOPVP MOPPP Indapyrophenidone MDPV Naphyrone PEP Picilorex Prolintane Pyrovalerone
Racetams	Oxiracetam Phenylpiracetam Phenylpiracetam hydrazide
Tropanes	4-fluorotropacocaine 4'-Fluorococaine Altropane (IACFT) Brasofensine CFT (WIN 35,428) β-CIT (RTI-55) Cocaethylene Cocaine Dichloropane (RTI-111) Difluoropine FE-β-CPPIT FP-β-CPPIT Ioflupane (¹²³I) Norcocaine PIT PTT RTI-31 RTI-32 RTI-51 RTI-112 RTI-113 RTI-120 RTI-121 (IPCIT) RTI-126 RTI-150 RTI-177 RTI-229 RTI-336 RTI-354 RTI-371 RTI-386 Salicylmethylecgonine Tesofensine Troparil (β-CPT, WIN 35,065-2) Tropoxane WF-23 WF-33
Tryptamines	4-HO-αMT 4-Methyl-αET 4-Methyl-αMT 5-Chloro-αMT 5-Fluoro-αMT 5-MeO-αET 5-MeO-αMT 5-MeO-DIPT 6-Fluoro-αMT 7-Methyl-αET αET αMT
Others	2-MDP 3,3-Diphenylcyclobutanamine Amfonelic acid Amineptine Amiphenazole Atipamezole Atomoxetine Bemegride Benzydamine BTQ BTS 74,398 Centanafadine Ciclazindol Clofenciclan Cropropamide Crotetamide D-161 Desipramine Diclofensine Dimethocaine Efaroxan Etamivan Fenisorex Fenpentadiol Gamfexine Gilutensin GSK1360707F GYKI-52895 Hexacyclonate Idazoxan Indanorex Indatraline JNJ-7925476 Lazabemide Leptacline Lomevactone LR-5182 Mazindol Meclofenoxate Medifoxamine Mefexamide Methamnetamine Methastyridone Methiopropamine Naphthylaminopropane Nefopam Nikethamide Nomifensine O-2172 Oxaprotiline PNU-99,194 PRC200-SS Rasagiline Rauwolscine Rubidium chloride Setazindol Tametraline Tandamine Thiopropamine Thiothinone Trazium UH-232 Yohimbine
ATC code:N06B

v t e ADHD pharmacotherapies
CNSTooltip central nervous systemstimulants	Amphetamine (Mixed amphetamine salts,Levoamphetamine,Dextroamphetamine,Lisdexamfetamine) Methamphetamine Methylphenidate Dexmethylphenidate Serdexmethylphenidate (+dexmethylphenidate)
Non-classical CNS stimulants	Armodafinil Atomoxetine Modafinil Viloxazine
α₂-adrenoceptor agonists	Clonidine Guanfacine
Antidepressants	Amitriptyline Bupropion Buspirone Desipramine Duloxetine Imipramine Milnacipran Moclobemide Nortriptyline Reboxetine Venlafaxine
Miscellaneous/others	Amantadine Carbamazepine
Related articles	Attention deficit hyperactivity disorder (ADHD) Attention deficit hyperactivity disorder management Hypokalemic sensory overstimulation Monoamine releasing agent Dopamine (DA) Dopamine transporter (DAT) Dopamine reuptake inhibitor (DRI) Norepinephrine (NE) Norepinephrine transporter (NET) Norepinephrine reuptake inhibitor (NRI) Serotonin (5-HT) Serotonin transporter (SERT) Selective serotonin reuptake inhibitor (SSRI) Serotonin-norepinephrine reuptake inhibitor (SNRI) Norepinephrine-dopamine reuptake inhibitor (NDRI) Serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI)

Monoamine reuptake inhibitors

DATTooltip Dopamine transporter
(DRIsTooltip Dopamine reuptake inhibitors)

Piperazines:DBL-583 GBR-12783 GBR-12935 GBR-13069 GBR-13098 JJC8-088 Nefazodone Vanoxerine
Piperidines:4-Fluoropethidine Benocyclidine (BTCP) Desoxypipradrol Dexmethylphenidate Difemetorex Ethylphenidate HDMP-28 Methylphenidate Pethidine (meperidine) Phencyclidine Pipradrol Serdexmethylphenidate Tenocyclidine
Pyrrolidines:Diphenylprolinol MDPV Naphyrone Prolintane Pyrovalerone
Tropanes:Altropane Benzatropine (benztropine) Brasofensine CFT Cocaine Dichloropane Difluoropine Etybenzatropine (ethybenztropine) FE-β-CPPIT FP-β-CPPIT Ioflupane (¹²³I) RTI-55 RTI-112 RTI-113 RTI-121 RTI-126 RTI-150 RTI-177 RTI-229 RTI-336 Tesofensine Troparil Tropoxane WF-11 WF-23 WF-31 WF-33
Others:Adrafinil Amifitadine Armodafinil Amfonelic acid Amineptine Ansofaxine BTQ BTS 74,398 Bupropion Chaenomeles speciosa Ciclazindol Dasotraline Desmethylsertraline Desmethylsibutramine (BTS-54354) Diclofensine Didesmethylsibutramine (BTS-54505) Dimethocaine Diphenylpyraline Dizocilpine (MK-801) DOV-102,677 DOV-216,303 Efavirenz Ephenidine Esketamine EXP-561 Fencamfamin Fezolamine Fluorenol GYKI-52895 Hydroxybupropion Indatraline Ketamine Lafadofensine Lefetamine Levophacetoperane Liafensine LR-5182 Manifaxine Mazindol Medifoxamine Mesocarb Metaphit MIN-117 (WF-516) Modafinil Nefopam Nomifensine NS-2359 O-2172 Oroxylin A Perafensine Pridefine Radafaxine Rimcazole Sertraline Sibutramine Solriamfetol Tametraline Tedatioxetine Threohydrobupropion Tripelennamine Venlafaxine

NETTooltip Norepinephrine transporter
(NRIsTooltip Norepinephrine reuptake inhibitors)

Selective norepinephrine reuptake inhibitors:Amedalin Alseroxylon Ciclazindol Daledalin Edivoxetine Esreboxetine Lortalamine Mazindol Nisoxetine Reboxetine Talopram Talsupram Tandamine Teniloxazine Viloxazine
Norepinephrine–dopamine reuptake inhibitors:Amineptine Bupropion Fencamine Fencamfamin Hydroxybupropion Lefetamine Levophacetoperane LR-5182 Manifaxine Methylphenidate Nomifensine O-2172 Radafaxine Serdexmethylphenidate Solriamfetol
Serotonin–norepinephrine reuptake inhibitors:Atomoxetine (tomoxetine) CP-39,332 Desvenlafaxine Duloxetine Eclanamine Levomilnacipran McN5652 Milnacipran N-Methyl-PPPA Nafenodone PPPA Tofenacin Venlafaxine
Serotonin–norepinephrine–dopamine reuptake inhibitors:3,3-Diphenylcyclobutanamine Amifitadine Ansofaxine Bicifadine Brasofensine Centanafadine Cocaine Dasotraline Desmethylsertraline Desmethylsibutramine (BTS-54354) Diclofensine Didesmethylsibutramine (BTS-54505) DOV-102677 DOV-216303 EXP-561 Fezolamine HDMP-28 HP-505 Indatraline JNJ-7925476 JZ-IV-10 Lafadofensine Liafensine Mazindol Naphyrone Nefazodone Nefopam NS-2359 Perafensine PRC200 Pridefine SEP-228431 SEP-228432 Sibutramine Tedatioxetine Tesofensine Threohydrobupropion Tropanes (e.g.,cocaine)
Tricyclic antidepressants:Amitriptyline Butriptyline Cianopramine Clomipramine Desipramine Dosulepin (dothiepin) Doxepin Imipramine Lofepramine Melitracen Nortriptyline Protriptyline Trimipramine
Tetracyclic antidepressants:Amoxapine Maprotiline Mianserin Oxaprotiline Setiptiline
Others:Antihistamines (e.g.,brompheniramine,chlorphenamine,pheniramine,tripelennamine) Antipsychotics (e.g.,loxapine,ziprasidone) Arylcyclohexylamines (e.g.,ketamine,phencyclidine) Dopexamine Ephenidine Ginkgo biloba Indeloxazine Nefazodone Opioids (e.g.,desmetramadol,methadone,pethidine (meperidine),tapentadol,tramadol,levorphanol)

SERTTooltip Serotonin transporter
(SRIsTooltip Serotonin reuptake inhibitors)

Selective serotonin reuptake inhibitors:6-Nitroquipazine Alaproclate Centpropazine Cericlamine Citalopram Dapoxetine Desmethylcitalopram Didesmethylcitalopram Escitalopram Femoxetine Fluoxetine Fluvoxamine Indalpine Ifoxetine Norfluoxetine Omiloxetine Panuramine Paroxetine PIM-35 Pirandamine RTI-353 Seproxetine Sertraline Zimelidine Selective serotonin reuptake inhibitors and serotonin receptor modulators:Etoperidone Litoxetine Lubazodone LY-393558 Quipazine SB-649915 TGBA01AD Trazodone Vilazodone Vortioxetine
Serotonin–norepinephrine reuptake inhibitors:Atomoxetine (tomoxetine) Bicifadine CP-39332 Desvenlafaxine Duloxetine Eclanamine Levomilnacipran McN5652 Milnacipran N-Methyl-PPPA PPPA Tofenacin Venlafaxine
Serotonin–norepinephrine–dopamine reuptake inhibitors:3,3-Diphenylcyclobutanamine Amifitadine Ansofaxine Bicifadine Brasofensine Centanafadine Cocaine Dasotraline Desmethylsertraline Desmethylsibutramine (BTS-54354) Diclofensine Didesmethylsibutramine (BTS-54505) DOV-102677 DOV-216303 EXP-561 Fezolamine HDMP-28 HP-505 Indatraline JNJ-7925476 JZ-IV-10 Lafadofensine Liafensine Mazindol Naphyrone Nefazodone Nefopam NS-2359 Perafensine PRC200 Pridefine SEP-228431 SEP-228432 Sibutramine Tedatioxetine Tesofensine Threohydrobupropion Tropanes (e.g.,cocaine)
Tricyclic antidepressants:Amitriptyline Cianopramine Clomipramine Cyanodothiepin Desipramine Dosulepin (dothiepin) Doxepin Imipramine Lofepramine Nortriptyline Pipofezine Protriptyline
Others:A-80426 Amoxapine Antihistamines (e.g.,brompheniramine,chlorphenamine,dimenhydrinate,diphenhydramine,mepyramine (pyrilamine),pheniramine,tripelennamine) Antipsychotics (e.g.,loxapine,ziprasidone) Arylcyclohexylamines (e.g.,3-MeO-PCP,esketamine,ketamine,methoxetamine,phencyclidine) Cyclobenzaprine Delucemine Dextromethorphan Dextrorphan Efavirenz Hypidone Medifoxamine Mesembrine Mifepristone MIN-117 (WF-516) N-Me-5-HT Opioids (e.g.,dextropropoxyphene,methadone,pethidine (meperidine),levorphanol,tapentadol,tramadol) Roxindole

VMATsTooltip Vesicular monoamine transporters

Others

Unsorted:Cendifensine

DAT enhancers:Luteolin

DAT modulators:Agonist-like:SoRI-9804
SoRI-20040;Antagonist-like:SoRI-20041

See also:Receptor/signaling modulators •Monoamine releasing agents •Adrenergics •Dopaminergics •Serotonergics •Monoamine metabolism modulators •Monoamine neurotoxins

Phenethylamines

Entactogens:Lophophine
MDPEA
MDMPEA

Amphetamines

Phentermines

Entactogens:MDPH
MDMPH

Others:Cericlamine

Cathinones

Phenylisobutylamines
(and further-extended)

Stimulants:α-Propylphenethylamine
Hexapradol
Phenylisobutylamine (α-ethylphenethylamine)

Catecholamines
(and close relatives)

Cyclized
phenethylamines

Phenylalkylpyrrolidines	α-PBP α-PHP α-PPP α-PVP MDPBP MDPPP MDPV 4-MePBP 4-MePHP 4-MePPP Fluorolintane MOPPP MOPVP MPBP MPHP MPPP Naphyrone PEP Prolintane Pyrovalerone
2-Benzylpiperidines (phenidates)	2-Benzylpiperidine 3-Bromomethylphenidate 3-Chloromethylphenidate 3-Methylmethylphenidate 3,4-Dichloro-2-benzylpiperidine 3,4-Dichloroethylphenidate 3,4-Dichloromethylphenidate 4-Bromoethylphenidate 4-Bromomethylphenidate 4-Chloromethylphenidate 4-Fluoroethylphenidate 4-Fluoroisopropylphenidate 4-Fluoromethylphenidate 4-Methyl-2-benzylpiperidine 4-Methylisopropylphenidate 4-Methylmethylphenidate 4-Nitromethylphenidate α-Acetyl-2-benzylpiperidine α-Keto-2-benzylpiperidine CPMBP Desoxypipradrol (2-DPMP) Difemetorex Ethylnaphthidate (HDEP-28) Ethylphenidate Isopropylnaphthidate Isopropylphenidate MDMPH Methylnaphthidate (HDMP-28) Methylphenidate Phacetoperane Pipradrol Propylphenidate Rimiterol Ritalinamide Ritalinic acid SCH-5472 Serdexmethylphenidate
Phenylmorpholines (phenmetrazines)	(2R,3R)-Hydroxybupropion 2-(2,5-Dimethoxy-4-bromophenyl)morpholine 2-Fluorophenmetrazine 2-Methylphenmetrazine 2-Phenylmorpholine 2-Phenyl-3,6-dimethylmorpholine 3-Chlorophenmetrazine (PAL-594) 3-Fluorophenetrazine 3-Fluorophenmetrazine (PAL-593) 3-Methoxyphenmetrazine 3-Methylphenmetrazine (PAL-773) 4-Fluorophenmetrazine (PAL-748) 4-Methylphendimetrazine 4-Methylphenmetrazine (PAL-747) 2C-B-morpholine Fenbutrazate Fenmetramide Flumexadol G-130 Isophenmetrazine Manifaxine Methylenedioxyphenmetrazine Morazone N-Ethylphenmetrazol Naphthylmetrazine (PAL-704) Naphthylmorpholine (PAL-678) Oxaflozane PDM-35 PF-219,061) Phendimetrazine Phenetrazine Phenmetetrazine Phenmetrazine Phenmetrazol Pseudophenmetrazine Radafaxine ((2S,3S)-hydroxybupropion)
Phenyloxazolamines (aminorexes)	3-Methylaminorex 4-Ethylaminorex (4-EAR) 4'-Fluoroaminorex 4-Methylaminorex (4-MAR) 4,4'-Dimethylaminorex (4,4'-DMAR) 2C-B-aminorex 2F-MAR 4B-MAR 4C-MAR 4F-MAR Aminorex Clominorex Cyclazodone Ephedroxane Fenozolone Fluminorex MDMAR Methylenedioxyaminorex (MDAR) N-Methylcyclazodone N,N-Dimethylaminorex Pemoline Thozalinone
Isoquinolines and tetrahydroisoquinolines	Anhalamine Anhalidine Anhalinine Anhalonidine Anhalonine Anhalotine Arizonine Calycotomine Carnegine (pectenine) Corypalline Debrisoquine Deglucopterocereine Deutetrabenazine Diclofensine DOB-CR DOM-CR Esproquin Gigantine Hedycarine Heliamine Hydrastinine Hydrocotarnine Hydrohydrastinine (MDMTHIQ; MDMA-CR) Isoanhalamine Isoanhalidine Isoanhalonidine Isocorypalline Isopellotine Isosalsoline Lemaireocereine Longimammamine Longimammatine Longimammidine Longimammosine Lophocerine Lophophorine Lophotine MDMA-CR Mescalotam N-Methylanhalinine N-Methylheliamine N-Methylisosalsoline N-Methyl-DOM-CR (Beatrice-CR) N-Methyl-THIQ (METH-CR) Nomifensine Norsalsolinol Nortehaunine Norweberine O-Methylanhalonidine O-Methylpellotine Pachycereine Pellotine Perafensine Peyoglutam Peyophorine Peyotine PMMA-CR Quinisocaine Reticuline Salsolidine Salsoline Salsolinol TDIQ (MDTHIQ, MDA-CR) Tehaunine TehaunineN-oxide Tepenine Tetrabenazine Tetrahydroisoquinoline (THIQ; AMPH-CR) Tetrahydropapaveroline Tilisolol Tretoquinol Uberine Valbenazine Weberidine Weberine Zelandopam
2-Aminoindanes	2-Aminoindane (2-AI) 5-IAI Aprindine BFAI BFMAI DHAI DOM-AI ETAI Indanorex Indantadol MDAI MDMAI MEAI (5-MeO-AI) MMAI NM-2-AI PNU-99,194 TAI
2-Aminotetralins	2-Aminotetralin (2-AT) 5-OH-DPAT 6-CAT 7-OH-DPAT 8-OH-DPAT AS-19 CHF-1024 DOM-AT MDAT MDMAT Nolomirole UH-232
Others / unsorted	1-Aminomethylindanes (e.g.,2CB-Ind,AMMI,bromojimscaline,jimscaline) 2-ADN 2-Benzhydrylpyrrolidine 2C-B-5-hemiFLY-α6 (BNAP) 2C-B-PYR 2CBecca 2CJP 2CLisaB 2CLisaH 3-Benzazepines (e.g.,fenoldopam,lorcaserin,7-chlorolorcaserin,SCHEMBL5334361) 3-Benzhydrylmorpholine 3-Phenylpiperidines (e.g.,3-phenylpiperidine,3-PPP,OSU-6162 (PNU-96391),LPH-5,LPH-48,Z3517967757 (Z7757)) 6-AB AL-1095 Aminochromes (e.g.,adrenochrome,adrenolutin) Benzocyclobutenes (e.g.,2CBCB-NBOMe,bromotomscaline,S33005,TCB-2,tomscaline) Benzoxepins (e.g.,BBOX,IBOX,TFMBOX) Butyltolylquinuclidine Camfetamine Cypenamine (trans-2-phenylcyclopentylamine) Diphenidine Diphenylprolinol DMBMPP Ergolines (e.g.,LSD) Fencamfamin GYKI-52895 HDMP-29 Ivabradine Methoxphenidine Methylmorphenate Milnacipran MT-45 2-Naphthylamine Org 6582 Partial ergolines (e.g.,NDTDI,RU-27849,DEIMDHPCA,DEMPDHPCA,DEMPDHPCA-2C-D,RU-27251) PF-592,379 Phenylcyclopropylamines (e.g.,DMCPA,TMT,tranylcypromine) Phenylpiracetams (e.g.,phenylpiracetam,MRZ-9547,RGPU-95) Pyridopyrroloquinoxalines (e.g.,lumateperone,deulumateperone,IHCH-7079,IHCH-7086,IHCH-7113,ITI-1549) Tetrahydrobenzopyranylamines (e.g.,CT-5126) Tolazoline Tricyclics (e.g.,AMDA,AMDH,benzoctamine,dizocilpine,SpAMDA) ZC-B

Related compounds

2-Furylethylamine
2-Pyrrolylethylamine
3-Pyrrolylethylamine
3-Pyrrolylpropylamine
2-Tetrahydrofurylethylamine
4-Benzylpiperidine
7-AB
Alkylamines (e.g.,1,3-DMBATooltip 1,3-dimethylbutylamine,1,4-DMAATooltip 1,4-dimethylamylamine,heptaminol,iproheptine,isometheptene,methylhexanamine/1,3-DMAA,octodrine,oenethyl,tuaminoheptane)
Benzylamines (e.g.,benzylamine,α-methylbenzylamine,MDM1EA,ALPHA,M-ALPHA,pargyline)
Benzylpiperazines (e.g.,benzylpiperazine,MDBZP,fipexide)
Cyclohexylaminopropanes (e.g.,propylhexedrine,norpropylhexedrine)
Cyclopentylaminopropanes (e.g.,isocyclamine,cyclopentamine)
Phenoxyethylamines (e.g.,3,4,5-trimethoxyphenoxyethylamine,CT-4719,ORG-37684)
Phenylalkenylamines (e.g.,phenylbutenamine)
Phenylalkynylamines (e.g.,phenylbutynamine)
Phenylpiperazines (e.g.,1-phenylpiperazine,mCPPTooltip meta-chlorophenylpiperazine,TFMPPTooltip trifluoromethylphenylpiperazine,oMPPTooltip ortho-methylphenylpiperazine,pFPPTooltip para-fluorophenylpiperazine,pMeOPPTooltip para-methoxyphenylpiperazine)
Phenylpropylamines (e.g.,phenylpropylamine,homo-MDA,homo-MDMA)
Thienylaminopropanes (thiopropamines) (e.g.,thiopropamine,methiopropamine,thiothinone)

v t e Chemical classes ofpsychoactive drugs
Stimulants	Amphetamine-type/dopamine releasing agents:Alkylamines Cycloalkylaminopropanes Arylpiperazines Benzylpiperazines Phenylpiperazines Phenethylamines Aminorexes/phenyloxazolamines Amphetamines/α-methylphenethylamines Cathinones/β-ketoamphetamines β-Hydroxyamphetamines/cathinols Naphthylaminopropanes Phentermines Phenylisobutylamines/α-ethylphenethylamines α-Propylphenethylamines Phenylmorpholines/phenmetrazines Thiopropamines/thienylaminopropanes Cocaine-type/typical dopamine reuptake inhibitors:Phenethylamines Phenidates/benzylpiperidines Phenylethylpyrrolidines Pyrrolidinophenones Phenyltropanes/cocaine analogues Modafinil-type/atypical dopamine reuptake inhibitors:Modafinil analogues Phenylpiracetams Caffeine-type/adenosine receptor antagonists:Xanthines/methylxanthines Nicotine-type/nicotinic acetylcholine receptor agonists:Nicotine analogues
Depressants	GABA_A receptor positive allosteric modulators:Alcohols/ethanol analogues Barbiturates Benzodiazepines Pyrrolobenzodiazepines Thienobenzodiazepines Thienodiazepines Thienotriazolodiazepines Triazolobenzodiazepines Carbamates Ethers Neuroactive steroids Nonbenzodiazepines β-Carbolines Cyclopyrrolones Imidazopyridines Pyrazolopyrimidines Phenols Piperidinediones Quinazolinones GABA_A receptor agonists:Isoxazoles GHB receptor agonists:1,4-Butanediols α₂δ subunit-containing voltage-gated calcium channel blockers:Gabapentinoids Opioids/μ-opioid receptor agonists:Benzimidazoles Nitazenes Fentanyl analogues/phenylpiperidines Mitragyna alkaloids Morphinans/phenanthrenes Opiates/opium alkaloids Utopioids Antihistamines/H₁ receptor antagonists:Benzimidazoles Diarylmethanes Ethylenediamines Tricyclics Dibenzocycloheptenes
Hallucinogens	Serotonergic psychedelics/serotonin 5-HT_2A receptor agonists:Arylpiperazines Phenylpiperazines Quinolinylpiperazines Cyclized phenethylamines 3-Benzazepines Cyclized tryptamines Azepinoindoles Ibogalogs Iboga alkaloids β-Carbolines Harmala alkaloids Ergolines Lysergamides Simplified/partial lysergamides Phenethylamines (methoxyphenethylamines) 2Cs 25-NB/NBOMes 2C-Os 2C-Ts HOT-x TWEETIOs Amphetamines/α-methylphenethylamines 3Cs Dimethoxyamphetamines/DMAs DOx Alephs Methylenedioxyamphetamines/MDxx Trimethoxyamphetamines/TMAs BOx FLYs/benzofurans Phenylisobutylamines/α-ethylphenethylamines 4Cs Scalines Ψ-PEAs Tryptamines α-Alkyltryptamines α-Alkyl-β-ketotryptamines 4-Hydroxytryptamines 5-Hydroxytryptamines 5-Methoxytryptamines Miscellaneous Dissociatives/NMDA receptor antagonists:Adamantanes Arylcyclohexylamines Diarylethylamines Morphinans κ-Opioid receptor agonists:Benzomorphans Salvinorins GABA_A receptor agonists:Isoxazoles Deliriants/anticholinergics/muscarinic acetylcholine receptor antagonists:Diarylmethanes Tropanes Others:Cyclized tryptamines Azepinoindoles Iboga alkaloids (Phyto)cannabinoids
Entactogens	Serotonin releasing agents:Phenethylamines Aminoindanes Aminotetralins Amphetamines Benzofuranylaminopropanes Benzothiophenylaminopropanes Ethylenedioxyamphetamines Indanylaminopropanes Indolylaminopropanes Methylenedioxyamphetamine/MDxx Tetralinylaminopropanes Tryptamines α-Alkyltryptamines Miscellaneous
Psychiatric drugs	Anxiolytics:Azapirones Benzodiazepines Pyrrolobenzodiazepines Thienobenzodiazepines Thienodiazepines Thienotriazolodiazepines Triazolobenzodiazepines Antidepressants:Tricyclic antidepressants Dibenzazepines Dibenzocycloheptenes Dibenzothiepins Dibenzoxazepines Dibenzoxepins Tetracyclic antidepressants Antipsychotics/dopamine D₂ receptor antagonists or partial agonists:Benzamides Benzimidazoles Benzisothiazoles Benzisoxazoles Butyrophenones Diphenylbutylpiperidines Phenylpiperazines Tricyclics Dibenzazepines Dibenzodiazepines Dibenzothiazepines Dibenzothiepins Dibenzoxazepines Phenothiazines Thienobenzodiazepines Mood stabilizers/anticonvulsants:Gabapentinoids Tricyclics Dibenzazepines Valproates
Others	Nootropics:Racetams Phenylpiracetams Miscellaneous:3-Benzazepines Adamantanes Catecholamines Tetrahydroisoquinolines Yohimbans