Chemistry:Propylamphetamine

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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 IC50 of 1,013 nM.[3] The drug can be N-dealkylated to form amphetamine (10–20% excreted in urine after 24 hours).[4][5] A study in rats found propylamphetamine to be approximately 4-fold less potent than amphetamine.[6][7]

Monoamine release of propylamphetamine and related agents (EC50, nM)
Compound NE DA 5-HT Ref
Phenethylamine 10.9 39.5 >10,000 [3][8][9]
d-Amphetamine 6.6–10.2 5.8–24.8 698–1,765 [10][11][9][12]
d-Methamphetamine 12.3–14.3 8.5–40.4 736–1,292 [10][13][9][12]
Ethylamphetamine ND 88.5 ND [3]
  d-Ethylamphetamine 28.8 44.1 333.0 [6][14]
Propylamphetamine ND RI (1,013) ND [3]
Butylamphetamine ND IA (>10,000) ND [3]
Notes: The smaller the value, the more strongly the drug releases the neurotransmitter. The assays were done in rat brain synaptosomes and human potencies may be different. See also Monoamine releasing agent § Activity profiles for a larger table with more compounds. Refs:[15][16]

See also

References

  1. ↑ "Amphetamine in rat brain after intraperitoneal injection of N-alkylated analogues". Progress in Neuro-Psychopharmacology & Biological Psychiatry 7 (4–6): 813–6. 1983. doi:10.1016/0278-5846(83)90073-8. PMID 6686713. 
  2. ↑ "Evaluation of internal standards for the analysis of amphetamine and methamphetamine". Journal of Analytical Toxicology 19 (6): 375–80. October 1995. doi:10.1093/jat/19.6.375. PMID 8926730. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 "Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter". Drug Alcohol Depend 147: 1–19. February 2015. doi:10.1016/j.drugalcdep.2014.12.005. PMID 25548026. 
  4. ↑ "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. doi:10.1111/j.2042-7158.1973.tb09943.x. PMID 4151673. 
  5. ↑ "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. doi:10.1111/j.2042-7158.1976.tb04063.x. PMID 11289. 
  6. ↑ 6.0 6.1 "Structure-activity relationships for locomotor stimulant effects and monoamine transporter interactions of substituted amphetamines and cathinones". Neuropharmacology 245. March 2024. doi:10.1016/j.neuropharm.2023.109827. PMID 38154512. "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. ↑ "Structure-activity relationships among some d-N-alkylated amphetamines". Pharmacology, Biochemistry, and Behavior 13 (6): 869–876. December 1980. doi:10.1016/0091-3057(80)90221-x. PMID 7208552. 
  8. ↑ Forsyth, Andrea N (22 May 2012). Synthesis and Biological Evaluation of Rigid Analogues of Methamphetamines. https://scholarworks.uno.edu/td/1436/. Retrieved 4 November 2024. 
  9. ↑ 9.0 9.1 9.2 "Dopamine-releasing agents". Dopamine Transporters: Chemistry, Biology and Pharmacology. Hoboken [NJ]: Wiley. July 2008. pp. 305–320. ISBN 978-0-470-11790-3. OCLC 181862653. https://bitnest.netfirms.com/external/Books/Dopamine-releasing-agents_c11.pdf. 
  10. ↑ 10.0 10.1 "Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin". Synapse 39 (1): 32–41. January 2001. doi:10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3. PMID 11071707. 
  11. ↑ "Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products". Neuropsychopharmacology 38 (4): 552–562. March 2013. doi:10.1038/npp.2012.204. PMID 23072836. 
  12. ↑ 12.0 12.1 "Profiling CNS Stimulants with a High-Throughput Assay for Biogenic Amine Transporter Substractes". Problems of Drug Dependence 1999: Proceedings of the 61st Annual Scientific Meeting, The College on Problems of Drug Dependence, Inc. NIDA Res Monogr. 180. 1999. pp. 1–476 (252). https://archives.nida.nih.gov/sites/default/files/180.pdf#page=261. "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). [...]" 
  13. ↑ "The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue". Neuropsychopharmacology 37 (5): 1192–1203. April 2012. doi:10.1038/npp.2011.304. PMID 22169943. 
  14. ↑ Nicole, Lauren (2022). "In vivo Structure-Activity Relationships of Substituted Amphetamines and Substituted Cathinones". https://www.proquest.com/openview/a207e98868b4a9c5ac9296fb24abbcd8/. "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. [...]" 
  15. ↑ "Monoamine transporters and psychostimulant drugs". European Journal of Pharmacology 479 (1–3): 23–40. October 2003. doi:10.1016/j.ejphar.2003.08.054. PMID 14612135. 
  16. ↑ "Therapeutic potential of monoamine transporter substrates". Current Topics in Medicinal Chemistry 6 (17): 1845–1859. 2006. doi:10.2174/156802606778249766. PMID 17017961. 



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