Quantitative differences in the pharmacological effects of (+)- and (−)-cathinone

Abstract

The optically pure isomers of cathinone were prepared by separating synthetic cathinone racemate and used to study central and peripheral effects of these indirect sympathomimetics in rats and guinea pigs. The (-)-isomer was significantly more potent than the (+)-isomer in stimulating locomotor activity whereas no difference was observed with respect to their cardiac effects. In analogy to observations with (+)- and (-)-amphetamine such variable isomer discrimination may be due to different stereoselectivities of amine uptake mechanisms in the target tissues.

Cathinone, a Natural Amphetamine

“…In discrimination experiments, the non-natural R( +)enantiomer of cathinone was found to be three times less potent than S( -)cathinone (Glennon et al 1984a;Schechter 1986b). The same potency ratio has been observed when evaluating the effects of the two enantiomers on the locomotor activity of rats (Gugelmann et al 1985) as well as in experiments determining the effect of the two enantiomers on the release of radioactivity from dopamine-prelabelled CNS tissue (Kalix 1986). This ratio is about the same as that prevailing for the two enantiomen of amphetamine, and thus, in this respect there is also analogy between cathinone and amphetamine.…”

“…Thus, cathinone potentiated constrictions of the isolated rabbit ear artery induced by field stimulation while having a potency similar to that of amphetamine (Knoll 1979). Furthermore, cathinone markedly increased blood pressure in anaesthetized rat and cat (Knoll 1979;Yanagita 1979), and had a positive chronotropic and inotropic effect on isolated guinea pig atria (Gugelmann et al 1985). These in vitro observations are consonant with an in vivo study on the cardiovascular effects of cathinone in anaesthetized dogs, in which cathinone and amphetamine caused practically the same dose-related increases in heart rate, blood pressure and cardiac contractile force.…”

“…It can be assumed that these movements interfere with locomotor activity, the interference explaining the bell shape of the dose-response curve mentioned above. For example, stereotyped oral activities such as compulsive chewing, gnawing and licking were observed after cathinone administration to rabbits (24 mg kg-' intravenously, Kalix 1980a), mice ( 1 1 mg kg-' intraperitoneally, Valterio & Kalix 1982) and rats (8.33 mg kg-' intraperitoneally, Gugelmann et al 1985). analyzed the stereotypical behaviour induced by cathinone in rats while comparing its effect to that of amphetamine and apomorphine.…”

Khat chewing, cardiovascular diseases and other internal medical problems: The current situation and directions for future research

“…Khat chewing by human volunteers increases blood pressure which coincides with elevated plasma levels of cathinone (Brenneisen et al, 1990;Widler et al, 1994), the peak occurring at 1.5-3.5 h (Halket et al, 1995). Cathinone increases blood pressure, has positive inotropic and chronotropic actions in isolated atria (Gugelmann et al, 1985) and increases heart rate in anaesthetized rats (Kalix and Braenden, 1985) and dogs (Kohli and Goldberg, 1982). Vasoconstriction from electrical field stimulation is potentiated and claimed to arise from enhanced noradrenaline release (Kalix, 1992).…”

Khat chewing and cardiovascular risk profile in a cohort of Yemeni patients with angiographically documented coronary artery disease

“…Centrally, cathinone causes hyperactivity, excitability, euphoria and restlessness 8. Peripheral (cardiovascular) effects include an increase in heart rate and blood pressure—in human volunteers—and a positive inotropic and chronotropic effect in isolated atria 10 11. Moreover, khat use was claimed as an independent risk factor for acute myocardial infarction (MI) 12.…”