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Naphthylaminopropane

Clinical data
Other names	NAP; Naphthylisopropylamine; NIPA; PAL-287; Naphetamine; Amnetamine; 1-(2-Naphthyl)-2-aminopropane; alpha-Methylnapthylethylamine; α-Methylnaphthylethylamine; 1-(α-Naphthyl)-2-aminopropane
Routes of administration	Oral
ATC code	None
Legal status
Legal status	In general: uncontrolled
Identifiers
IUPAC name 1-(Naphthalen-2-yl)propan-2-amine
CAS Number	18085-03-5
PubChem CID	10219723
ChemSpider	8395215
UNII	53PF675WUK
CompTox Dashboard (EPA)	DTXSID70630474
Chemical and physical data
Formula	C13H15N
Molar mass	185.270 g·mol
3D model (JSmol)	Interactive image
SMILES CC(N)Cc2ccc1ccccc1c2

Naphthylaminopropane (NAP; code name PAL-287), also known as naphthylisopropylamine (NIPA), is an experimental drug that was under investigation for the treatment of alcohol and stimulant addiction.

Pharmacology

Naphthylaminopropane acts as a non-neurotoxic releasing agent of serotonin, norepinephrine, and dopamine (i.e., as an SNDRATooltip serotonin–norepinephrine–dopamine releasing agent), with EC₅₀Tooltip half-maximal effective concentration values for monoamine release of 3.4 nM, 11.1 nM, and 12.6 nM, respectively. It is also an agonist of the serotonin 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors (EC₅₀ = 466 nM, 40 nM, and 2.3 nM, respectively). The drug acts as a full agonist of the serotonin 5-HT_2B and 5-HT_2A receptors and as a weak partial agonist of the serotonin 5-HT_2C receptor (E_maxTooltip maximal efficacy = 20%).

In animal studies, naphthylaminopropane was shown to reduce cocaine self-administration, yet produced relatively weak stimulant effects when administered alone, being a much less effective stimulant than dextroamphetamine. Further research was being conducted in primates to see if the drug would be a useful substitute for treating drug addiction in humans.

An important observation is that in behavioral studies, rodents would consistently self-administer selective norepinephrine–dopamine releasing agents (NDRAs) like dextroamphetamine, yet compounds that also potently release serotonin like naphthylaminopropane would not be self-administered. In addition to the drug's effects on self-administration, the available evidence suggests that the locomotor activation caused by dopamine releasers is also dampened when they additionally induce serotonin release. Notably, despite potent dopamine release induction, naphthylaminopropane produces weak or no locomotor activation in rodents.

The high affinity of naphthylaminopropane for the serotonin 5-HT_2C receptor meant that it might function as an appetite suppressant and was being considered for possible clinical use for this indication (i.e., weight loss). However, concerns were raised over the affinity of the drug for the serotonin 5-HT_2B receptor, since some of the more serious side effects of the serotonin-releasing weight loss drug fenfluramine were linked to activation of this receptor. It is uncertain, although was considered unlikely per the researchers who developed the drug, that activation of the serotonin 5-HT_2A and 5-HT_2B receptors occurs to a significant degree in vivo.

Naphthylaminopropane has been found to act as a potent monoamine oxidase A (MAO-A) inhibitor, with an IC₅₀Tooltip half-maximal inhibitory concentration of 420 nM. This is similar to the potency of the well-known MAO-A inhibitors para-methoxyamphetamine (PMA) and 4-methylthioamphetamine (4-MTA).

Chemistry

Naphthylaminopropane was first described in the scientific literature by 1939. The drug is also known as 1-naphthylaminopropane (1-NAP) or α-naphthylaminopropane, and it was described along with its positional isomer 2-naphthylaminopropane (2-NAP; β-naphthylaminopropane). Both 1-NAP and 2-NAP failed to substitute for dextroamphetamine in rodent drug discrimination tests, suggesting that they lack psychostimulant-like effects. The β-keto and N-methyl analogue of 2-NAP has been assessed and was found to act as a potent SNDRA similarly to naphthylaminopropane.

Naphthylaminopropane is structurally related to certain rigid analogues of amphetamine. Rigid amphetamine analogues include 2-aminotetralin (2-AT), 2-amino-1,2-dihydronaphthalene (2-ADN), 1-phenylpiperazine (1-PP), 2-aminoindane (2-AI), 6-ABTooltip 6-amino-6,7,8,9-tetrahydro-5H-benzocycloheptene, and 7-ABTooltip 7-amino-6,7,8,9-tetrahydro-5H-benzocycloheptene.

A few derivatives of naphthylaminopropane have been developed or have appeared, including methamnetamine (N-methylnaphthylaminopropane; MNAP; PAL-1046), N-ethylnaphthylaminopropane (ENAP; PAL-1045), and BMAPN (βk-methamnetamine; β-keto-MNAP; 2-naphthylmethcathinone). Like naphthylaminopropane, these derivatives also act as potent monoamine releasing agents, including of serotonin, norepinephrine, and/or dopamine.

See also

• 5-APDI
• 6-APT
• HDEP-28
• HDMP-28
• Naphyrone

References

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• Drugs not assigned an ATC code
• 5-HT2A agonists
• 5-HT2B agonists
• 5-HT2C agonists
• Amines
• Designer drugs
• Entactogens and empathogens
• Monoamine oxidase inhibitors
• 2-Naphthyl compounds
• Serotonin-norepinephrine-dopamine releasing agents
• Stimulants