Naphthylaminopropane

Naphthylaminopropane

Systematic (IUPAC) name
(±)-1-(2-naphthyl)propan-2-amine
Clinical data
Pregnancy cat.	?
Legal status	Uncontrolled
Routes	Oral
Identifiers
CAS number	18085-03-5
ATC code	None
PubChem	CID 10219723
ChemSpider	8395215
Synonyms	1-(2-naphthyl)-2-aminopropane; alpha-methylnapthylethylamine
Chemical data
Formula	C13H15N
Mol. mass	185.27 g/mol
SMILES CC(N)Cc2ccc1ccccc1c2

Naphthylisopropylamine (PAL-287) is an experimental drug currently under investigation for the treatment of alcohol and stimulant addiction.^[1]

Naphthylisopropylamine acts as a non-neurotoxic^[2] releasing agent of serotonin, norepinephrine, and dopamine, with EC₅₀ values of 3.4 nM, 11.1 nM, and 12.6 nM, respectively.^[3] It also has affinity for the 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors (EC₅₀ values = 466 nM, 40 nM, and 2.3 nM, respectively),^[1] and acts as a full agonist at 5-HT_2B and as a partial agonist at 5-HT_2C, while its affinity for 5-HT_2A is probably too low to be significant.^[1]

In animal studies, naphthylisopropylamine was shown to reduce cocaine self-administration, yet produced relatively weak stimulant effects when administered alone, being a (much) lesser stimulant than d-amphetamine for comparison.^[2][4][5] Further research is now being conducted in primates to see if it will be a useful substitute for treating drug addiction in humans as well.^[6]

An important observation is that in behavioral studies, rodents would consistently self-administer selective norepinephrine and dopamine releasing agents such as d-amphetamine, yet compounds that also release serotonin like naphthylisopropylamine would not be self-administered.^[2] In addition to the drugs (acute) effects on self-administration, all of the available evidence suggests that the locomotor activation caused by the majority of dopamine releasers is also dampened when the drugs also cause 5HTergic release.^[7] In fact, PAL-287 causes no locomotor activation at all (although admittedly the tests were only after acute dosing).

The high affinity of PAL-287 for 5-HT_2C receptors meant that it functioned as a reliable anorectant and was being considered for this indication (i.e. weight loss). However, there were ultimately some concerns raised over the compounds affinity for 5HT_2B receptors, since some of the more serious side effects of the serotonin releasing weight loss drug fenfluramine were linked to an activation of this receptor.^[8] Apparently, more research will have to be done to assess if PAL-287 causes activation of the 5HT_2A and 5HT_2B receptors in vivo. However, according to the authors, even the relatively safe drug MDMA causes heart disease,^[9] and the incidence being reported for fenfluramine was not that great, even though the evidence being presented was indisputable.^[8] Thus it is relatively more likely that any of the more serious side effects from using PAL-287 will only occur in cases of overdose, and not when using a clinically responsible amount of the drug.

See also

• 5-APDB
• 6-APB
• 6-APDB
• 5-(2-Aminopropyl)indole
• Ethylenedioxymethamphetamine
• Indanylaminopropane
• Tetralinylaminopropane
• Naphyrone

References