Chemistry:Phenylpropylamine

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Phenylpropylamine, also known as 3-phenylpropylamine, is a monoamine releasing agent (MRA) related to phenethylamine (2-phenylethylamine).[1][2] It is the analogue of phenethylamine in which the ethylamine side chain has been lengthened by one carbon atom to instead be a propylamine chain.[1][2]

Phenylpropylamine was synthesized and characterized during investigations of the structure–activity relationships (SAR) of phenethylamine and amphetamine MRAs.[1][2] It acts as a norepinephrine–dopamine releasing agent (NDRA).[1][2] However, phenylpropylamine is dramatically less potent than phenethylamine as an NDRA in rat brain synaptosomes in vitro and shows ~7-fold preference for induction of norepinephrine release over dopamine release.[1][2]

The analogue of phenethylamine with the ethylamine side chain shortened by one carbon atom to instead be a methylamine chain is benzylamine (phenylmethylamine).[3] In contrast to phenethylamine and phenylpropylamine, benzylamine is said to be inactive as a norepinephrine releasing agent (NRA).[3] However, certain derivatives of benzylamine have nonetheless been found to show MRA-like effects in animals.[4][5] In addition, benzylpiperazine, an analogue of benzylamine with a methylamine-like side chain, is a potent MRA and psychostimulant.[6][2][7]

Monoamine release of phenylpropylamine and related agents (EC50, nM)
Compound NE DA 5-HT Ref
Phenethylamine (2-phenylethylamine) 10.9 39.5 >10,000 [8][1][2]
Phenylpropylamine (3-phenylpropylamine) 222 1,491 ND [1][2]
β-Methylphenethylamine (2-phenylpropylamine) 126 627 ND [9]
Dextroamphetamine (d-phenylisopropylamine) 6.6–7.2 5.8–24.8 698–1,765 [10][11]
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:[12][6]

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Synthesis and Biological Evaluation of Rigid Analogues of Methamphetamines. 22 May 2012. https://scholarworks.uno.edu/td/1436/. Retrieved 4 November 2024. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 "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. 
  3. ↑ 3.0 3.1 "Amphetamines: Structure-Activity Relationships". Stimulants. Boston, MA: Springer US. 1978. pp. 1–39. doi:10.1007/978-1-4757-0510-2_1. ISBN 978-1-4757-0512-6. "The β-phenethylamine skeleton is a critical feature of the molecule since either increasing or decreasing the number of carbons between the phenyl ring and the nitrogen reduced or abolished the activity. Both the γ-phenylpropylamines (e.g., 1-phenyl-3-aminobutane, γ-phenylpropylamine, γ-phenyl-N,N-dimethylpropylamine) and the benzylamines (e.g., α-methylbenzylamine, N,N-diethylbenzylamine, benzylamine) were found to be inactive as releasers of norepinephrine (Daly et al., 1966)." 
  4. ↑ The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. 1. Berkeley: Transform Press. 2011. ISBN 978-0-9630096-3-0. 
  5. ↑ "Behavioral and developmental effects of two 3,4-methylenedioxymethamphetamine (MDMA) derivatives". Drug Alcohol Depend 36 (3): 161–166. December 1994. doi:10.1016/0376-8716(94)90141-4. PMID 7889806. 
  6. ↑ 6.0 6.1 "Therapeutic potential of monoamine transporter substrates". Current Topics in Medicinal Chemistry 6 (17): 1845–1859. 2006. doi:10.2174/156802606778249766. PMID 17017961. https://zenodo.org/record/1235860. 
  7. ↑ "1-Benzylpiperazine and other piperazine-based stimulants". Novel Psychoactive Substances. Elsevier. 2022. pp. 301–332. doi:10.1016/b978-0-12-818788-3.00009-7. ISBN 978-0-12-818788-3. 
  8. ↑ "Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter". Drug and Alcohol Dependence 147: 1–19. February 2015. doi:10.1016/j.drugalcdep.2014.12.005. PMID 25548026. 
  9. ↑ "The Supplement Adulterant β-Methylphenethylamine Increases Blood Pressure by Acting at Peripheral Norepinephrine Transporters". J Pharmacol Exp Ther 369 (3): 328–336. June 2019. doi:10.1124/jpet.118.255976. PMID 30898867. 
  10. ↑ "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. 2013. doi:10.1038/npp.2012.204. PMID 23072836. 
  12. ↑ "Monoamine transporters and psychostimulant drugs". Eur J Pharmacol 479 (1–3): 23–40. October 2003. doi:10.1016/j.ejphar.2003.08.054. PMID 14612135. 




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