Chlorphentermine

Clinical data
Other names	4-Chlorophentermine; 4-Chloro-α-methylamphetamine; 4-Chloro-α,α-dimethylphenethylamine
Routes of administration	Oral
Drug class	Serotonin releasing agent;Anorectic
ATC code	A08AA (WHO)
Legal status
Legal status	BR: Class A3 (Psychoactive drugs)[1] CA: Schedule IV UK: Class C US: Schedule III (but withdrawn from the market)
Pharmacokinetic data
Eliminationhalf-life	40 hours[2]–5 days[3]
Identifiers
IUPAC name 1-(4-chlorophenyl)-2-methylpropan-2-amine
CAS Number	461-78-9 Y 151-06-4
PubChemCID	10007
DrugBank	DB01556 Y
ChemSpider	9613 Y
UNII	NHW07912O7
KEGG	C07559 Y
ChEMBL	ChEMBL1201269 Y
CompTox Dashboard(EPA)	DTXSID0022806
ECHA InfoCard	100.006.651
Chemical and physical data
Formula	C10H14ClN
Molar mass	183.68 g·mol−1
3D model (JSmol)	Interactive image
SMILES Clc1ccc(cc1)CC(N)(C)C
InChI InChI=1S/C10H14ClN/c1-10(2,12)7-8-3-5-9(11)6-4-8/h3-6H,7,12H2,1-2H3 Y Key:ZCKAMNXUHHNZLN-UHFFFAOYSA-N Y
(verify)

Chlorphentermine, sold under the brand namesApsedon,Desopimon, andLucofen, is aserotonergicappetite suppressant of theamphetamine family. Developed in 1962, it is thepara-chloroderivative of the better-known appetite suppressantphentermine, which is still in current use.

The drug acts as a highlyselectiveserotonin releasing agent (SRA).^[4] It is not apsychostimulant and has little or nomisuse potential, but is classed as aSchedule III drug in the United States due mainly to its similarity to other appetite suppressants such asdiethylpropion which have been more widely misused. It is no longer used due mainly tosafety concerns, as it has a serotonergic effects profile similar to other withdrawn appetite suppressants such asfenfluramine andaminorex which were found to causepulmonary hypertension andcardiac fibrosis following prolonged use.^[5]

Chlorphentermine was firstsynthesized by 1954 and was subsequently developed in the early 1960s.^[6][7][8][9] It remained on the market in the United States as late as 2004.^[10]

Chlorphentermine was used as anappetite suppressant for purposes ofweight loss in people withoverweightness orobesity.^[11][3][12]

Side effects of chlorphentermine includeimpaired sleep,irritability, andgastrointestinal symptoms includingdyspepsia.^[11]

Euphoria is said to occasionally occur with chlorphentermine, but to a much lesser extent than withdextroamphetamine.^[3] The drug does not produceamphetamine-like subjective effects in humans^[13][14] and thepsychostimulant effects of chlorphentermine are described as much less than those of dextroamphetamine.^[3]

Chlorphentermine acts as aselectiveserotonin releasing agent (SSRA).^[25][26][18] TheEC₅₀Tooltip half-maximal effective concentration for monoamine release with chlorphentermine are 30.9 nM forserotonin, >10,000 nM fornorepinephrine, and 2,650 nM fordopamine.^[25][26][18] Although it is inactive as a norepinephrine releasing agent, it is a moderatelypotentnorepinephrine reuptake inhibitor (IC₅₀Tooltip half-maximal inhibitory concentration = 451 nM; 15-fold lower than itsEC₅₀ value for serotonin release).[27]^[26] The activity of chlorphentermine as an SSRA is in contrast tophentermine, which acts as a selectivenorepinephrine and dopamine releasing agent (NDRA).^[26][18]

In animals, chlorphentermine robustly anddose-dependently increasesserotonin levels in the brain.^[23][14] It also increasesdopamine levels in the brain at high doses.^[23][14] Whereasdextroamphetamine andphentermine robustlystimulate locomotor activity and areself-administered in animals, chlorphentermine does not increase locomotor activity and is either not self-administered or is only weakly self-administered.^[28][13][14] Conversely, it has been reported that chlorphentermine weakly stimulates locomotor activity at low doses and progressively suppresses it at higher doses.^[29] In contrast to other amphetamines, it does not producestereotypies nor reversereserpine-induced behavioral depression.^[29] In addition, unlikepara-chloroamphetamine (PCA), chlorphentermine does not produce thehead-twitch response, a behavioral proxy ofpsychedelic effects, in animals.^[29]

In contrast tofenfluramine andnorfenfluramine, chlorphentermine shows negligible activity as anagonist of theserotonin5-HT_2A,5-HT_2B, and5-HT_2C receptors.^[26] ItsEC₅₀ values at these receptors are >10,000 nM, 5,370 nM, and 6,456 nM, respectively.[26] TheseEC₅₀ values are >324-fold, 164-fold, and 209-fold lower than itsEC₅₀ value in inducing serotonin release, respectively.[26]

Despite its lack of direct agonism at the serotonin 5-HT_2B receptors, chlorphentermine shows induction ofprimary pulmonary hypertension inanimal models.^[26][3] This suggests that serotonin release can induce this form of toxicity without concomitant direct serotonin 5-HT_2B receptor agonism.^[26] However, other findings seem to contradict this hypothesis, for instance increases in serotonin levels with fenfluramine and other serotonin-elevating drugs being inadequate for inducing cardiac valvulopathy-like changes, and instead implicating additional direct serotonin 5-HT_2B receptor agonism in this toxicity.^[30] It has been said that it is possible that anactive metabolite of chlorphentermine might show greater serotonin 5-HT_2B receptor agonism than chlorphentermine itself, analogously to the case of fenfluramine andnorfenfluramine, and that this possibility should be examined.^[26]

The amphetamine homologue of chlorphentermine, PCA, is apotentserotonergic neurotoxin.^[31] In contrast to PCA, preliminary animal experiments suggest that chlorphentermine is non-neurotoxic, although more research in this area is still needed.^[31]

Theelimination half-life of chlorphentermine is relatively long and is stated to be 40 hours^[2] and about 5 days by different sources.^[3]

Chlorphentermine, also known as 4-chlorophentermine, 4-chloro-α-methylamphetamine, and 4-chloro-α,α-dimethylphenethylamine, is asubstituted phenethylamine andamphetaminederivative.^[23] It is thepara-chloroanalogue ofphentermine.^[23] Chlorphentermine is also closely structurally related to certain other phentermines includingcericlamine,cloforex,clortermine,etolorex, andmethylenedioxyphentermine (MDPH). It is closely structurally related to the amphetamine derivativespara-chloroamphetamine (PCA) andpara-chloromethamphetamine (PCMA) as well.^[32]

Chlorphentermine was first described in thescientific literature by 1954.^[6][7][8][9] It was subsequently developed for use as an appetite suppressant in the early 1960s.^[6][7][8][9] The drug is said to have beenwithdrawn from the market in the United States in 1969^[33] and in the United Kingdom in 1974.^[3] However, other sources indicate that chlorphentermine continued to be marketed in the United States as late as 2004.^[10][34]Pulmonary toxicity of chlorphentermine was observed in animals by the early 1970s and this resulted in reservations about its clinical use.^[3]

• 4-Chlorophenyl compounds
• Anorectics
• Carbonic anhydrase activators
• Cardiotoxins
• Phentermines
• Respiratory toxins
• Serotonin releasing agents
• Withdrawn drugs

• CS1 Brazilian Portuguese-language sources (pt-br)
• Articles with short description
• Short description is different from Wikidata
• ECHA InfoCard ID from Wikidata