Thiopropamine Explained

Thiopropamine is a stimulant drug which is an analogue of amphetamine where the phenyl ring has been replaced by thiophene. It has similar stimulant effects to amphetamine but with around one third the potency. The N-methyl and thiophen-3-yl analogues are also known and are somewhat more potent, though still generally weaker than the corresponding amphetamines.^{[1] [2]}

Pharmacology

Like amphetamine and most of its analogues, thiopropamine most likely is a norepinephrine–dopamine reuptake inhibitor and/or releasing agent.

Thiopropamine is likely to be metabolized into active 4-hydroxymethiopropamine and thiophene S-oxides.^{[3] [4]} These are further deaminated by CYP2C in liver transforming them into inactive 1-(Thiophen-2-yl)-2-propan-2-one which is a phenylacetone derivative.^[5] Propan-2-amines are not metabolized by monoamine oxidases and most actually behave as competitive monoamine oxidase inhibitors.^{[6] [7]}

Notes and References

1. Comparative Physiological Actions of Phenyl-, Thienyl- and Furylisopropylamines . Alles GA, Feigen GA . Journal of Pharmacology and Experimental Therapeutics . July 1941 . 72 . 3 . 265–75.
2. 3-Substituted Thiophenes. VIII. 3-Thienylalkylamines . September 1954 . Campaigne E, McCarthy WC . Journal of the American Chemical Society . 76 . 17 . 4466–4468 . 10.1021/ja01646a054 .
3. 10.1021/ja962466g . Chemical and Biological Oxidation of Thiophene: Preparation and Complete Characterization of Thiophene S-Oxide Dimers and Evidence for Thiophene S-Oxide as an Intermediate in Thiophene Metabolism in Vivo and in Vitro . February 1997 . Treiber A, Dansette PM, El Amri H, Girault JP, Ginderow D, Mornon JP, Mansuy D . Journal of the American Chemical Society . 119 . 7 . 1565–1571.
4. Dansette PM, Thang DC, el Amri H, Mansuy D . Evidence for thiophene-S-oxide as a primary reactive metabolite of thiophene in vivo: formation of a dihydrothiophene sulfoxide mercapturic acid . Biochemical and Biophysical Research Communications . 186 . 3 . 1624–30 . August 1992 . 1510686 . 10.1016/S0006-291X(05)81594-3 .
5. Yamada H, Shiiyama S, Soejima-Ohkuma T, Honda S, Kumagai Y, Cho AK, Oguri K, Yoshimura H . 6 . Deamination of amphetamines by cytochromes P450: studies on substrate specificity and regioselectivity with microsomes and purified CYP2C subfamily isozymes . The Journal of Toxicological Sciences . 22 . 1 . 65–73 . February 1997 . 9076658 . 10.2131/jts.22.65 . free .
6. Mantle TJ, Tipton KF, Garrett NJ . Inhibition of monoamine oxidase by amphetamine and related compounds . Biochemical Pharmacology . 25 . 18 . 2073–7 . September 1976 . 985546 . 10.1016/0006-2952(76)90432-9 .
7. Miller HH, Shore PA, Clarke DE . In vivo monoamine oxidase inhibition by d-amphetamine . Biochemical Pharmacology . 29 . 10 . 1347–54 . May 1980 . 6901611 . 10.1016/0006-2952(80)90429-3 .