Amfonelic acid

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Summary

Amfonelic acid (AFA), also known as WIN 25,978, is a research compound characterized by its dopaminergic stimulant effects and potential antibiotic properties. While clinical trials are scarce, their predominant application lies within scientific research.

Identifiers
IUPAC name
CAS Number15180-02-6 
PubChem CID2137
ChemSpider2052 
UNIIRR302AR19Y
KEGGD02897 
ChEMBLChEMBL35337 
CompTox Dashboard (EPA)DTXSID40164877
Chemical and physical data
FormulaC18H16N2O3
Molar mass308.337 g·mol−1

History

The discovery of AFA’s stimulant properties occurred serendipitously during research on the antibiotic nalidixic acid at Sterling-Winthrop. While initially studied for its antibiotic qualities, it became apparent that derivatives of nalidixic acid could have either stimulating or depressant effects on the central nervous system. AFA, in particular, exhibited higher potency and a more favorable therapeutic index than cocaine or amphetamine, leading to its selection for further investigation. Several clinical trials were conducted in the 1970s; however, the discovery that AFA exacerbated psychotic symptoms in schizophrenic patients and produced undesirable stimulant effects in geriatric depressives resulted in the discontinuation of clinical evaluation. Despite this, AFA continues to be widely employed as a valuable tool in pharmacological research to study the brain’s reward system, dopamine pathways, and the dopamine transporter. Since 2013, AFA has been available on the gray market, and there are numerous anecdotal reports of its non-medical use.

Pharmacological

In research studies, AFA has demonstrated potent and highly selective dopamine reuptake inhibition (DRI) in rat brain preparations. It exhibits a moderately long half-life of approximately 12 hours and boasts a dopaminergic potency roughly 50 times that of methylphenidate in rat brain preparations. Despite the absence of direct serotonin activity, rats treated with subchronic AFA doses experience subsequent decreases in 5HT and 5HIAA. AFA does not exhibit activity in the norepinephrine system.

Despite its distinct mechanism of action, AFA exhibits discriminatory substitution, with 150% of the stimulant potency of dextroamphetamine. AFA has shown neuroprotective properties against methamphetamine-induced damage to dopamine neurons and enhances the effects of antipsychotic drugs such as haloperidol, trifluoperazine, and spiperone. Rats have been observed to self-administer AFA in a dose-dependent manner.

While AFA’s discovery occurred in the context of antibiotic research, there is limited data on its antimicrobial activity. In 1988, biologist G.C. Crumplin noted, “[AFA] is less active against bacteria than many other 4-quinolones, but studies in our laboratory have revealed its marked toxicity to selected mammalian cell lines when compared to more effective antibacterial agents among 4-quinolones. Additionally, sublethal doses have induced significant alterations in protein patterns produced by the cells, suggesting a potential impact on gene transcription in mammalian cells.” When assessed through broth microdilution, AFA exhibited a MIC of 125 μg/mL for Escherichia coli, a concentration thirty times higher than the MIC of nalidixic acid in the same E. coli strain.

FAQ

  • What is Amfonelic Acid?
  • Amfonelic Acid is a chemical compound known for its dopaminergic stimulant effects and potential antibiotic properties. It was initially discovered during antibiotic research.
  • How was Amfonelic Acid discovered?
  • The stimulant properties of Amfonelic Acid were discovered serendipitously during research on the antibiotic nalidixic acid at Sterling-Winthrop.
  • Is Amfonelic Acid used as a pharmaceutical drug?
  • Amfonelic Acid is not commonly used as a pharmaceutical drug. It is primarily employed for research purposes.
  • What are the stimulant effects of Amfonelic Acid?
  • Amfonelic Acid acts as a potent dopamine reuptake inhibitor and has a stimulant effect on the central nervous system. It exhibits discriminatory substitution with stimulant potency similar to dextroamphetamine.
  • Is Amfonelic Acid associated with any therapeutic applications?
  • Although Amfonelic Acid has shown neuroprotective properties against methamphetamine-induced damage to dopamine neurons, its clinical evaluation was discontinued due to undesirable side effects in certain patient populations.
  • Is Amfonelic Acid used in scientific research?
  • Amfonelic Acid remains a valuable pharmacological tool for studying the brain’s reward system, dopamine pathways, and the dopamine transporter in scientific research.
  • Is Amfonelic Acid available for non-medical use?
  • Since 2013, Amfonelic Acid has been available on the gray market, and there are anecdotal reports of its non-medical use. However, the legality and safety of such use can vary by region.
  • What is the antibiotic activity of Amfonelic Acid?
  • There is limited data available regarding the antimicrobial activity of Amfonelic Acid. While initially discovered during antibiotic research, its effectiveness against bacteria appears lower than other antibiotics.
  • Are there any potential side effects or risks associated with Amfonelic Acid use?
  • The side effects and risks of Amfonelic Acid use, particularly in non-medical contexts, are not well-documented. It is essential to approach substances like this cautiously and consult with healthcare professionals when necessary.
  • Where can I find more information about Amfonelic Acid?
  • To access more comprehensive information about Amfonelic Acid, consult scientific literature and trustworthy sources. When seeking information online, ensure that the sources are reliable and credible.

References

    1. Morris H (October 2015). “Sad Pink Monkey Blues.” Published in Harper’s Magazine. Retrieved on September 19, 2015.
    2. US patent 3590036: “Naphthyridine-3-carboxylic Acids, Their Derivatives and Preparation Thereof.”
    3. Aceto MD, Botton I, Martin R, Levitt M, Bentley HC, Speight PT (1970). “Pharmacologic properties and mechanism of action of amfonelic acid.” Published in the European Journal of Pharmacology, Volume 10, Issue 3, Pages 344–354.
    4. Fuller RW, Perry KW, Bymaster FP, Wong DT (March 1978). “Comparative effects of pemoline, amfonelic acid, and amphetamine on dopamine uptake and release in vitro and on brain 3,4-dihydroxyphenylacetic acid concentration in spiperone-treated rats.” Published in The Journal of Pharmacy and Pharmacology, Volume 30, Issue 3, Pages 197–198.
    5. McMillen BA, Shore PA (July 1978). “Amfonelic acid, a non-amphetamine stimulant, has marked effects on brain dopamine metabolism but not noradrenaline metabolism: association with differences in neuronal storage systems.” Published in The Journal of Pharmacy and Pharmacology, Volume 30, Issue 7, Pages 464–466.
    6. Izenwasser S, Werling LL, Cox BM (June 1990). “Comparison of the effects of cocaine and other inhibitors of dopamine uptake in rat striatum, nucleus accumbens, olfactory tubercle, and medial prefrontal cortex.” Published in Brain Research, Volume 520, Issues 1–2, Pages 303–309.
    7. McMillen BA, Scott SM, Williams HL (1991). “Effects of subchronic amphetamine or amfonelic acid on rat brain dopaminergic and serotonergic function.” Published in the Journal of Neural Transmission. General Section, Volume 83, Issues 1–2, Pages 55–66.
    8. Agmo A, Belzung C, Rodríguez C (1997). “A rat model of distractibility: effects of drugs modifying dopaminergic, noradrenergic, and GABAergic neurotransmission.” Published in the Journal of Neural Transmission, Volume 104, Issue 1, Pages 11–29.
    9. Aceto MD, Rosecrans JA, Young R, Glennon RA (April 1984). “Similarity between (+)-amphetamine and amfonelic acid.” Published in Pharmacology, Biochemistry, and Behavior, Volume 20, Issue 4, Pages 635–637.
    10. Pu C, Fisher JE, Cappon GD, Vorhees CV (June 1994). “The effects of amfonelic acid, a dopamine uptake inhibitor, on methamphetamine-induced dopaminergic terminal degeneration and astrocytic response in rat striatum.” Published in Brain Research, Volume 649, Issues 1–2, Pages 217–224.
    11. Waldmeier PC, Huber H, Heinrich M, Stoecklin K (January 1985). “Discrimination of neuroleptics by means of their interaction with amfonelic acid: an attempt to characterize the test.” Published in Biochemical Pharmacology, Volume 34, Issue 1, Pages 39–44.
    12. Porrino LJ, Goodman NL, Sharpe LG (November 1988). “Intravenous self-administration of the indirect dopaminergic agonist amfonelic acid by rats.” Published in Pharmacology, Biochemistry, and Behavior, Volume 31, Issue 3, Pages 623–626.
    13. Crumplin GC (1988). “Aspects of chemistry in the development of the 4-quinolone antibacterial agents.” Published in Reviews of Infectious Diseases, Volume 10, Supplement 1, Pages S2-S9.

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