Phenylpropylamine

Last updated

Phenylpropylamine
3-Phenylpropylamine.svg
Clinical data
Other names3-Phenyl-1-propylamine
Drug class Norepinephrine–dopamine releasing agent
Identifiers
  • 3-phenylpropan-1-amine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.016.376 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C9H13N
Molar mass 135.210 g·mol−1
3D model (JSmol)
  • C1=CC=C(C=C1)CCCN
  • InChI=1S/C9H13N/c10-8-4-7-9-5-2-1-3-6-9/h1-3,5-6H,4,7-8,10H2
  • Key:LYUQWQRTDLVQGA-UHFFFAOYSA-N

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 Tooltip Half maximal effective concentration, nM)
Compound NE Tooltip Norepinephrine DA Tooltip Dopamine 5-HT Tooltip SerotoninRef
Phenethylamine (2-phenylethylamine)10.939.5>10,000 [8] [1] [2]
Phenylpropylamine (3-phenylpropylamine)2221,491ND [1] [2]
β-Methylphenethylamine (2-phenylpropylamine)126627ND [9]
Dextroamphetamine (d-phenylisopropylamine)6.6–7.25.8–24.8698–1,765 [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 2 3 4 5 6 7 Forsyth AN (22 May 2012). "Synthesis and Biological Evaluation of Rigid Analogues of Methamphetamines". ScholarWorks@UNO. Retrieved 4 November 2024.
  2. 1 2 3 4 5 6 7 8 Blough B (July 2008). "Dopamine-releasing agents" (PDF). In Trudell ML, Izenwasser S (eds.). Dopamine Transporters: Chemistry, Biology and Pharmacology. Hoboken [NJ]: Wiley. pp. 305–320. ISBN   978-0-470-11790-3. OCLC   181862653. OL   18589888W.
  3. 1 2 Biel JH, Bopp BA (1978). "Amphetamines: Structure-Activity Relationships". Stimulants. Boston, MA: Springer US. 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. ↑ Shulgin A, Manning T, Daley PF (2011). The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds . Vol. 1. Berkeley: Transform Press. ISBN   978-0-9630096-3-0.
  5. ↑ Bronson ME, Barrios-Zambrano L, Jiang W, Clark CR, DeRuiter J, Newland MC (December 1994). "Behavioral and developmental effects of two 3,4-methylenedioxymethamphetamine (MDMA) derivatives". Drug Alcohol Depend. 36 (3): 161–166. doi:10.1016/0376-8716(94)90141-4. PMID   7889806.
  6. 1 2 Rothman RB, Baumann MH (2006). "Therapeutic potential of monoamine transporter substrates". Current Topics in Medicinal Chemistry. 6 (17): 1845–1859. doi:10.2174/156802606778249766. PMID   17017961.
  7. ↑ Gee P, Schep LJ (2022). "1-Benzylpiperazine and other piperazine-based stimulants". Novel Psychoactive Substances. Elsevier. pp. 301–332. doi:10.1016/b978-0-12-818788-3.00009-7. ISBN   978-0-12-818788-3.
  8. ↑ Reith ME, Blough BE, Hong WC, Jones KT, Schmitt KC, Baumann MH, et al. (February 2015). "Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter". Drug and Alcohol Dependence. 147: 1–19. doi:10.1016/j.drugalcdep.2014.12.005. PMC   4297708 . PMID   25548026.
  9. ↑ Schindler CW, Thorndike EB, Rice KC, Partilla JS, Baumann MH (June 2019). "The Supplement Adulterant β-Methylphenethylamine Increases Blood Pressure by Acting at Peripheral Norepinephrine Transporters". J Pharmacol Exp Ther. 369 (3): 328–336. doi:10.1124/jpet.118.255976. PMC   6533570 . PMID   30898867.
  10. ↑ Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, et al. (January 2001). "Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin". Synapse. 39 (1): 32–41. doi:10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3. PMID   11071707.
  11. ↑ Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, et al. (2013). "Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products". Neuropsychopharmacology. 38 (4): 552–562. doi:10.1038/npp.2012.204. PMC   3572453 . PMID   23072836.
  12. ↑ Rothman RB, Baumann MH (October 2003). "Monoamine transporters and psychostimulant drugs". Eur J Pharmacol. 479 (1–3): 23–40. doi:10.1016/j.ejphar.2003.08.054. PMID   14612135.


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