Propylamphetamine Explained

Propylamphetamine (code name PAL-424; also known as N-propylamphetamine or NPA) is a psychostimulant of the amphetamine family which was never marketed. It was first developed in the 1970s, mainly for research into the metabolism of,^[1] and as a comparison tool to, other amphetamines.^[2]

Propylamphetamine is inactive as a dopamine releasing agent in vitro and instead acts as a low-potency dopamine reuptake inhibitor with an of 1,013nM.^[3] The drug can be N-dealkylated to form amphetamine (10–20% excreted in urine after 24hours).^{[4] [5]} A study in rats found propylamphetamine to be approximately 4-fold less potent than amphetamine.^{[6] [7]}

See also

• Methamphetamine
• Ethylamphetamine
• Isopropylamphetamine
• Butylamphetamine
• Phenylpropylaminopentane

Notes and References

1. Nazarali AJ, Baker GB, Coutts RT, Pasutto FM . Amphetamine in rat brain after intraperitoneal injection of N-alkylated analogues . Progress in Neuro-Psychopharmacology & Biological Psychiatry . 7 . 4–6 . 813–6 . 1983 . 6686713 . 10.1016/0278-5846(83)90073-8 . 35531794 .
2. Valtier S, Cody JT . Evaluation of internal standards for the analysis of amphetamine and methamphetamine . Journal of Analytical Toxicology . 19 . 6 . 375–80 . October 1995 . 8926730 . 10.1093/jat/19.6.375 .
3. Reith ME, Blough BE, Hong WC, Jones KT, Schmitt KC, Baumann MH, Partilla JS, Rothman RB, Katz JL . Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter . Drug Alcohol Depend . 147 . 1–19 . February 2015 . 25548026 . 10.1016/j.drugalcdep.2014.12.005 . 4297708 .
4. Beckett AH, Shenoy EV . The effect of N-alkyl chain length of stereochemistry on the absorption, metabolism and during excretion of N-alkylamphetamines in man . J Pharm Pharmacol . 25 . 10 . 793–799 . October 1973 . 4151673 . 10.1111/j.2042-7158.1973.tb09943.x .
5. Coutts RT, Dawson GW, Beckett AH . In vitro metabolism of 1-phenyl-2-(n-propylamino) propane (N-propylamphetamine) by rat liver homogenates . J Pharm Pharmacol . 28 . 11 . 815–821 . November 1976 . 11289 . 10.1111/j.2042-7158.1976.tb04063.x .
6. Fitzgerald LR, Gannon BM, Walther D, Landavazo A, Hiranita T, Blough BE, Baumann MH, Fantegrossi WE . Structure-activity relationships for locomotor stimulant effects and monoamine transporter interactions of substituted amphetamines and cathinones . Neuropharmacology . 245 . 109827 . March 2024 . 38154512 . 10.1016/j.neuropharm.2023.109827 . Although the number of amphetamine analogues with different amine substituents is relatively low in recreational drug markets (Cho and Segal, 1994), N-methyl and N-ethyl substitutions are sometimes found. Pharmacological activity of amphetamine-type drugs is decreased substantially if the N-alkyl chain is lengthened beyond ethyl, as previous studies show that N-propylamphetamine and N-butylamphetamine are ~4-fold and ~6-fold less potent than amphetamine in rats (Woolverton et al., 1980)..
7. Woolverton WL, Shybut G, Johanson CE . Structure-activity relationships among some d-N-alkylated amphetamines . Pharmacology, Biochemistry, and Behavior . 13 . 6 . 869–876 . December 1980 . 7208552 . 10.1016/0091-3057(80)90221-x . 10.1.1.687.9187 . 25123820 .