4-Fluoroamphetamine

From Wikipedia, the free encyclopedia
Jump to: navigation, search
4-Fluoroamphetamine
4-fluoroamphetamine.svg
Ball-and-stick model of the 4-fluoroamphetamine molecule
Systematic (IUPAC) name
(RS)-1-(4-Fluorophenyl)propan-2-amine
Clinical data
Pregnancy
category
  • N
Routes of
administration
oral
Identifiers
CAS Registry Number 459-02-9 N
PubChem CID: 9986
ChemSpider 9592 YesY
Chemical data
Formula C9H12FN
Molecular mass 153.20 g/mol
 N (what is this?)  (verify)

4-Fluoroamphetamine (4-FA; 4-FMP; PAL-303; "Flux"), also known as para-fluoroamphetamine (PFA) is a psychoactive research chemical of the phenethylamine and substituted amphetamine chemical classes. It produces stimulant and entactogenic effects. As a recreational drug, 4-FA is sometimes sold along with related compounds such as 2-fluoroamphetamine and 4-fluoromethamphetamine.[1][2]

Effects[edit]

The subjective effects of 4-fluoroamphetamine include euphoria which some find similar to the effects of MDMA, increased energy (stimulation), mood elevation, feelings of warmth and empathy, excessive talking, bruxism, and suppressed appetite (anorexic). The general course of effects involves primarily empathogenic effects for the first few hours, which fades out as increased stimulation develops over the next several hours.[medical citation needed]

The dopamine reuptake inhibition produced by 4-FA is stronger than that of either 4-CA or 4-IA.[3] 4-FA also produces less hyperthermia than similar compounds such as PMA, 3-MTA and 4-methylamphetamine.[medical citation needed]

Common acute side effects are nausea, headaches, increased heart rate and insomnia.[medical citation needed]

Neurotoxicity[edit]

4-FA does not cause long-lasting depletion of brain serotonin, unlike its analogs 4-CA and 4-BA.[4] This is thought to "reflect the inability of the fluoro-compound to be metabolized in the same way as the other haloamphetamines."[5]

Neurotoxicity does not increase down the series of para-halogenated amphetamine derivatives, even though serotonin releasing potency does follow this trend. For example, 4-iodoamphetamine is less toxic than is 4-chloroamphetamine.[3][6] Hence, this property is not related to serotonin releasing potency as such, since PAL-287 was reported to be not at all neurotoxic even though it is a powerful 5-HT releasing agent.[7] It is unclear where 4-methylamphetamine fits in on the neurotoxicity scale. The extensive serotonergic neurotoxicity of 4-chloroamphetamine (and its brominated derivative), and the increased serotonergic toxicity of 4-methylamphetamine[8] suggest that para-substitution seems to increase overall serotonergic (neuro)toxicity, compared to amphetamine. Exceptions include 4-MTA, a para-substituted, non-neurotoxic amphetamine.[9][10][11]

Pharmacology[edit]

4-Fluoroamphetamine is a releasing agent and reuptake inhibitor of dopamine, serotonin, and norepinephrine.[citation needed] The respective EC50 values are 2.0 x 10−7 M, 7.3 x 10−7 M, and 0.37 x 10−7 M, while the IC50 values are 7.7 x 10−7 M, 68 x 10−7 M, and 4.2 x 10−7 M.[2]

Regarding the metabolic fate of 4-FA, the C-F bond at the 4-position on the phenyl ring likely resists deactivation in the liver by cytochrome P450 oxidase.[12]

Toxicology[edit]

The LD50 (mouse; i.p.) of 4-FA is 46 mg/kg.[13]

See also[edit]

References[edit]

  1. ^ Rösner, P; Quednow, B; Girreser, U; Junge, T (2005). "Isomeric fluoro-methoxy-phenylalkylamines: a new series of controlled-substance analogues (designer drugs)". Forensic Science International 148 (2–3): 143–56. doi:10.1016/j.forsciint.2004.05.003. PMID 15639609. 
  2. ^ a b Nagai, F; Nonaka, R; Satoh Hisashi Kamimura, K (2007). "The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain". European Journal of Pharmacology 559 (2–3): 132–7. doi:10.1016/j.ejphar.2006.11.075. PMID 17223101. 
  3. ^ a b Marona-Lewicka, D; Rhee, GS; Sprague, JE; Nichols, DE (1995). "Psychostimulant-like effects of p-fluoroamphetamine in the rat". European Journal of Pharmacology 287 (2): 105–13. doi:10.1016/0014-2999(95)00478-5. PMID 8749023. 
  4. ^ Harvey, J. A. (1978). "Neurotoxic Action of Halogenated Amphetamines". Annals of the New York Academy of Sciences 305: 289–304. doi:10.1111/j.1749-6632.1978.tb31530.x. PMID 81648. 
  5. ^ Fuller, R. W.; Baker, J. C.; Perry, K. W.; Molloy, B. B. (1975). "Comparison of 4-chloro-, 4-bromo- and 4-fluoroamphetamine in rats: Drug levels in brain and effects on brain serotonin metabolism". Neuropharmacology 14 (10): 739–746. doi:10.1016/0028-3908(75)90099-4. PMID 1196472. 
  6. ^ Nichols, DE; Johnson, MP; Oberlender, R (1991). "5-Iodo-2-aminoindan, a nonneurotoxic analogue of p-iodoamphetamine". Pharmacology, Biochemistry, and Behavior 38 (1): 135–9. doi:10.1016/0091-3057(91)90601-W. PMID 1826785. 
  7. ^ Rothman, R. B.; Blough, BE; Woolverton, WL; Anderson, KG; Negus, SS; Mello, NK; Roth, BL; Baumann, MH (2005). "Development of a Rationally Designed, Low Abuse Potential, Biogenic Amine Releaser That Suppresses Cocaine Self-Administration". Journal of Pharmacology and Experimental Therapeutics 313 (3): 1361–1369. doi:10.1124/jpet.104.082503. PMID 15761112. 
  8. ^ Blanckaert, P.; van Amsterdam, Jgc; Brunt, Tm; van den Berg, Jdj; Van Durme, F.; Maudens, K.; van Bussel, Jch (2013-09-01). "4-Methyl-amphetamine: a health threat for recreational amphetamine users". Journal of Psychopharmacology (Oxford, England) 27 (9): 817–822. doi:10.1177/0269881113487950. ISSN 1461-7285. PMID 23784740. 
  9. ^ Huang, X.; Marona-Lewicka, D.; Nichols, D. E. (1992). "P-methylthioamphetamine is a potent new non-neurotoxic serotonin-releasing agent". European journal of pharmacology 229 (1): 31–38. doi:10.1016/0014-2999(92)90282-9. PMID 1473561. 
  10. ^ Li, Q; Murakami, I; Stall, S; Levy, AD; Brownfield, MS; Nichols, DE; Van De Kar, LD (1996). "Neuroendocrine pharmacology of three serotonin releasers: 1-(1,3-benzodioxol-5-yl)-2-(methylamino)butane (MBDB), 5-methoxy-6-methyl-2-aminoindan (MMAi) and p-methylthioamphetamine (MTA)". The Journal of Pharmacology and Experimental Therapeutics 279 (3): 1261–7. PMID 8968349. 
  11. ^ Murphy, J; Flynn, JJ; Cannon, DM; Guiry, PJ; McCormack, P; Baird, AW; McBean, GJ; Keenan, AK (2002). "In vitro neuronal and vascular responses to 5-hydroxytryptamine: modulation by 4-methylthioamphetamine, 4-methylthiomethamphetamine and 3,4-methylenedioxymethamphetamine". European Journal of Pharmacology 444 (1–2): 61–7. doi:10.1016/S0014-2999(02)01586-8. PMID 12191583. 
  12. ^ Fisher MB, Henne KR, Boer J (2006). "The complexities inherent in attempts to decrease drug clearance by blocking sites of CYP-mediated metabolism". Current Opinion in Drug Discovery & Development 9 (1): 101–9. PMID 16445122. 
  13. ^ E. Costa and S. Garattini (1970). Amphetamines and Related Compounds. New York: Raven Press. p. 28. 

External links[edit]