Azacyclonol Explained

Azacyclonol (trade names Ataractan, Calmeran, Frenoton, Frenquel, Psychosan), also known as γ-pipradrol, is a drug which is an ataractive; an agent which diminishes hallucinations in psychotic individuals.^{[1] [2]} It has also been called a tranquilizer and antipsychotic, though these definitions are not accurate as it does not actually possess such properties. Despite being a positional isomer of pipradrol, it is not a psychostimulant, and instead has mild depressant effects.^{[1] [3]}

The drug was introduced in Europe in the mid-1950s for the treatment of schizophrenia likely because it was found to attenuate the subjective psychedelic effects of LSD and mescaline in humans.^{[1] [4]} However, due to poor and mixed clinical effectiveness,^[4] it never gained widespread acceptance and was eventually discontinued.

Azacyclonol is also known as diphenylmethanolpiperidine and is the parent structure of the antihistamines fexofenadine and terfenadine. Terfenadine produces azacyclonol as a major active metabolite.^[5]

It is made by the organometallic addition of 4-bromopyridine to benzophenone, followed by catalytic hydrogenation of the pyridine heteroaromatic ring system to the corresponding piperidine.^[6]

Notes and References

1. BRAUN DL, BROWN BB, FELDMAN RG . The pharmacologic activity of alpha-(4-piperidyl)-benzhydrol hydrochloride (azacyclonol hydrochloride); an ataractive agent . The Journal of Pharmacology and Experimental Therapeutics . 118 . 2 . 153–61 . October 1956 . 13368052 . 2010-04-16 . 2019-12-08 . https://web.archive.org/web/20191208002146/http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=13368052 . dead .
2. Book: Swiss Pharmaceutical Society . Index Nominum 2000: International Drug Directory (Book with CD-ROM) . Medpharm Scientific Publishers . Boca Raton . 2000 . 3-88763-075-0 .
3. FARRANT J . Interactions between cocaine, tyramine and noradrenaline at the noradrenaline store . . 20 . 3. 540–9 . June 1963 . 13944436 . 1703814 . 10.1111/j.1476-5381.1963.tb01491.x.
4. FORSTER W, HENDERSON AL . A clinical study of Frenquel (alpha (4-piperidyl) benzhydrol hydrochloride) in chronic schizophrenia . Canadian Medical Association Journal . 76 . 2 . 97–101 . January 1957 . 13383414 . 1823487 .
5. Martens J . Determination of the terfenadine metabolite azacyclonol in human serum using gas chromatography-mass spectrometry . Journal of Chromatography B . 678 . 2 . 349–53 . April 1996 . 8738042 . 10.1016/0378-4347(95)00561-7.
6. Campen Jr Marcus G Van, Pogge Raymond C, Schumann Edward L; Wm S Merrell Co; (1957).