Naphthylaminopropane (PAL-287) is an experimental

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...

under investigation as of 2007 for the treatment of

alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...

and

stimulant Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...

addiction. Naphthylisopropylamine acts as a non- neurotoxic releasing agent of

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...

, norepinephrine, and

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

, with EC₅₀ values of 3.4 nM, 11.1 nM, and 12.6 nM, respectively. 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), 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. In animal studies, naphthylisopropylamine was shown to reduce cocaine

self-administration Self-administration is, in its medical sense, the process of a subject administering a pharmacological substance to themself. A clinical example of this is the subcutaneous "self-injection" of insulin by a diabetic patient. In animal experimentati ...

, yet produced relatively weak stimulant effects when administered alone, being a (much) lesser stimulant than

d-amphetamine Dextroamphetamine is a central nervous system (CNS) stimulant and an amphetamine enantiomer that is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance and c ...

for comparison. 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. 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. 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 serotonergic release. 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. 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, and the incidence being reported for fenfluramine was not that great, even though the evidence being presented was indisputable. 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.

References

{{Phenethylamines Amines 2-Naphthyl compounds Serotonin receptor agonists Serotonin-norepinephrine-dopamine releasing agents Stimulants Designer drugs Entactogens and empathogens

See also

References