Propylamphetamine

Last updated
Propylamphetamine
N-Propylamphetamine.svg
Propylamphetamine molecule ball.png
Clinical data
Other namesN-Propylamphetamine; NPA; PAL-424
ATC code
  • none
Legal status
Legal status
  • UK:Not controlled
Pharmacokinetic data
Metabolism Hepatic
Excretion Renal
Identifiers
  • N-(1-methyl-2-phenylethyl)propan-1-amine
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard 100.215.934 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C12H19N
Molar mass 177.291 g·mol−1
3D model (JSmol)
  • NC(C)Cc1ccccc1CCC
  • InChI=1S/C12H19N/c1-3-6-11-7-4-5-8-12(11)9-10(2)13/h4-5,7-8,10H,3,6,9,13H2,1-2H3 Yes check.svgY
  • Key:VMVXCJCVBKWYTF-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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 Tooltip half-maximal inhibitory concentration 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 Tooltip Half maximal effective concentration, nM)
Compound NE Tooltip Norepinephrine DA Tooltip Dopamine 5-HT Tooltip SerotoninRef
Phenethylamine 10.939.5>10,000 [3] [8] [9]
d-Amphetamine 6.6–10.25.8–24.8698–1,765 [10] [11] [9] [12]
d-Methamphetamine 12.3–14.38.5–40.4736–1,292 [10] [13] [9] [12]
Ethylamphetamine ND88.5ND [3]
   d-Ethylamphetamine 28.844.1333.0 [6] [14]
Propylamphetamine NDRI (1,013)ND [3]
Butylamphetamine NDIA (>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. ↑ Nazarali AJ, Baker GB, Coutts RT, Pasutto FM (1983). "Amphetamine in rat brain after intraperitoneal injection of N-alkylated analogues". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 7 (4–6): 813–6. doi:10.1016/0278-5846(83)90073-8. PMID   6686713. S2CID   35531794.
  2. ↑ Valtier S, Cody JT (October 1995). "Evaluation of internal standards for the analysis of amphetamine and methamphetamine". Journal of Analytical Toxicology. 19 (6): 375–80. doi:10.1093/jat/19.6.375. PMID   8926730.
  3. 1 2 3 4 5 Reith ME, Blough BE, Hong WC, Jones KT, Schmitt KC, Baumann MH, Partilla JS, Rothman RB, Katz JL (February 2015). "Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter". Drug Alcohol Depend. 147: 1–19. doi:10.1016/j.drugalcdep.2014.12.005. PMC   4297708 . PMID   25548026.
  4. ↑ Beckett AH, Shenoy EV (October 1973). "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. doi:10.1111/j.2042-7158.1973.tb09943.x. PMID   4151673.
  5. ↑ Coutts RT, Dawson GW, Beckett AH (November 1976). "In vitro metabolism of 1-phenyl-2-(n-propylamino) propane (N-propylamphetamine) by rat liver homogenates". J Pharm Pharmacol. 28 (11): 815–821. doi:10.1111/j.2042-7158.1976.tb04063.x. PMID   11289.
  6. 1 2 Fitzgerald LR, Gannon BM, Walther D, Landavazo A, Hiranita T, Blough BE, Baumann MH, Fantegrossi WE (March 2024). "Structure-activity relationships for locomotor stimulant effects and monoamine transporter interactions of substituted amphetamines and cathinones". Neuropharmacology. 245: 109827. doi:10.1016/j.neuropharm.2023.109827. PMC   10842458 . 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. ↑ Woolverton WL, Shybut G, Johanson CE (December 1980). "Structure-activity relationships among some d-N-alkylated amphetamines". Pharmacology, Biochemistry, and Behavior. 13 (6): 869–876. CiteSeerX   10.1.1.687.9187 . doi:10.1016/0091-3057(80)90221-x. PMID   7208552. S2CID   25123820.
  8. ↑ Forsyth, Andrea N (22 May 2012). "Synthesis and Biological Evaluation of Rigid Analogues of Methamphetamines". ScholarWorks@UNO. Retrieved 4 November 2024.
  9. 1 2 3 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.
  10. 1 2 Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS (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. S2CID   15573624.
  11. ↑ Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, Rothman RB, Goldberg SR, Lupica CR, Sitte HH, Brandt SD, Tella SR, Cozzi NV, Schindler CW (March 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. 1 2 Partilla JS, Dersch CM, Baumann MH, Carroll FI, Rothman RB (1999). "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 (PDF). NIDA Res Monogr. Vol. 180. pp. 1–476 (252). PMID   11680410. 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. ↑ Baumann MH, Ayestas MA, Partilla JS, Sink JR, Shulgin AT, Daley PF, Brandt SD, Rothman RB, Ruoho AE, Cozzi NV (April 2012). "The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue". Neuropsychopharmacology. 37 (5): 1192–1203. doi:10.1038/npp.2011.304. PMC   3306880 . PMID   22169943.
  14. ↑ Nicole, Lauren (2022). "In vivo Structure-Activity Relationships of Substituted Amphetamines and Substituted Cathinones". ProQuest. Retrieved 5 December 2024. 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. ↑ Rothman RB, Baumann MH (October 2003). "Monoamine transporters and psychostimulant drugs". European Journal of Pharmacology. 479 (1–3): 23–40. doi:10.1016/j.ejphar.2003.08.054. PMID   14612135.
  16. ↑ 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.
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