Thesubstituted naphthylethylamines are a class ofchemical compounds based onnaphthalene. Many naphthylethylamines arenaphthylaminopropanes (also known asnaphthylisopropylamines) due to the presence of amethyl group at thealpha carbon of thealkylchain. The naphthylethylamines arederivatives of thephenethylamines, while the naphthylaminopropanes are derivatives of theamphetamines.
There are two types of naphthylethylamines based onpositional isomerism: 1-naphthylethylamines and 2-naphthylethylamines. Examples of these include1-naphthylaminopropane (1-NAP) and2-naphthylaminopropane (2-NAP), respectively.
The substituted napthylethylamines include the following compounds:[1][2][3]
Additional naphthylethylamines include4-NEMD,centanafadine (EB-1020),nafimidone,naphazoline, andxaliproden (SR-57746). Somesynthetic cannabinoids such asTHJ-018 andTHJ-2201 are also naphthylethylamines.
Some related compounds that are not technically naphthylethylamines include1-naphthylpiperazine and its derivatives likeCSP-2503,F-11,461,S-14506, andS-14671. Another related compound is2-naphthylpiperazine.DMNPC is a 2-naphthylpiperidine.
Many naphthylethylamines, like2-naphthylaminopropane andderivatives, act asmonoamine releasing agents (MRAs),monoamine reuptake inhibitors (MRIs), and/ormonoamine receptor modulators.[1][5]Naphthylpropylaminopentane (NPAP) is amonoaminergic activity enhancer (MAE).[4] Some, such as 2-naphthylaminopropane and to a lesser extent1-naphthylaminopropane, but not others, such as NPAP, are also variablypotentmonoamine oxidase inhibitors (MAOIs).[3][4]
| Compound | NETooltip Norepinephrine | DATooltip Dopamine | 5-HTTooltip Serotonin | Ref |
|---|---|---|---|---|
| d-Amphetamine | 6.6–10.2 | 5.8–24.8 | 698–1,765 | [6][7][8][9][10] |
| 1-Naphthylaminopropane | ND | ND | ND | ND |
| 2-Naphthylaminopropane (NAP; PAL-287) | 11.1 | 12.6 | 3.4 | [11][8] |
| d-Methamphetamine | 12.3–14.3 | 8.5–40.4 | 736–1,292 | [6][12][8][10] |
| Methylnaphthylaminopropane (MNAP; PAL-1046) | 34 | 10 | 13 | [13][14] |
| l-Methcathinone | 13.1 | 14.8 | 1,772 | [15][9] |
| 1-Naphthylmethcathinone (AMAPN) | 92% at 10 μM | 55 | 21 | [2][16] |
| 2-Naphthylmethcathinone (BMAPN; βk-MNAP) | 94% at 10 μM | 34 | 27 | [2][16] |
| d-Ethylamphetamine | 28.8 | 44.1 | 333.0 | [17][18] |
| Ethylnaphthylaminopropane (ENAP; PAL-1045) | 137 | 46a | 12a | [13] |
| 2-Phenylmorpholine (PAL-632) | 79 | 86 | 20,260 | [5] |
| Naphthylmorpholine (PAL-678) | 88% at 10 μM | 79% at 10 μM | 92% at 10 μM | [5] |
| Phenmetrazine | 29–50.4 | 70–131 | 7,765–>10,000 | [19][8][20][5] |
| Naphthylmetrazine (PAL-704) | 203 | 111 | RI (105) | [5] |
| Notes: The smaller the value, the more strongly the drug releases the neurotransmitter. Theassays were done in rat brainsynaptosomes and humanpotencies may be different. See alsoMonoamine releasing agent § Activity profiles for a larger table with more compounds.Footnotes:aENAPTooltip Ethylnaphthylaminopropane is apartial releaser of serotonin (EmaxTooltip maximal efficacy = 66%) and dopamine (Emax = 78%).Refs:[21][22] | ||||
RESULTS. Methamphetamine and amphetamine potently released NE (IC50s = 14.3 and 7.0 nM) and DA (IC50s = 40.4 nM and 24.8 nM), and were much less potent releasers of 5-HT (IC50s = 740 nM and 1765 nM). Phentermine released all three biogenic amines with an order of potency NE (IC50 = 28.8 nM)> DA (IC50 = 262 nM)> 5-HT (IC50 = 2575 nM). Aminorex released NE (IC50 = 26.4 nM), DA (IC50 = 44.8 nM) and 5-HT (IC50 = 193 nM). Chlorphentermine was a very potent 5-HT releaser (IC50 = 18.2 nM), a weaker DA releaser (IC50 = 935 nM) and inactive in the NE release assay. Chlorphentermine was a moderate potency inhibitor of [3H]NE uptake (Ki = 451 nM). Diethylpropion, which is self-administered, was a weak DA uptake inhibitor (Ki = 15 µM) and NE uptake inhibitor (Ki = 18.1 µM) and essentially inactive in the other assays. Phendimetrazine, which is self-administered, was a weak DA uptake inhibitor (IC50 = 19 µM), a weak NE uptake inhibitor (8.3 µM) and essentially inactive in the other assays.
FIGURE 2-6: Release: Effects of the specified test drug on monoamine release by DAT (red circles), NET (blue squares), and SERT (black traingles) in rat brain tissue. [...] EC50 values determined for the drug indicated within the panel. [...]