Serotonin receptor affinity of cathinone and related analogs

Abstract

A series of cathinone (alpha-aminopropiophenone) analogues was examined using the isolated rat fundus preparation. (S)-(-)-Cathinone possesses twice the serotonin receptor affinity of (+/-)-cathinone and four times the affinity of racemic amphetamine. Several derivatives of cathinone were found to either possess a lower affinity than the parent compound or did not interact with the receptors in a competitive manner. Several novel analogues, 1-(aminomethyl)-3,4-dihydronaphthalene hydrochloride (3), 4-(aminomethyl)-3-chromene hydrochloride (4b), as well as its 6-methoxy derivative, a, interact with serotonin receptors but in a fashion which is, most likely, dissimilar to the interaction of the substituted cathinone analogues.

Effect of the Alkaloid (–)-Cathinone on the Release of Radioactivity from Rat Striatal Tissue Prelabelled with ³H-Serotonin

“…however, indications in the literature that interaction with serotoninergic neurons might be a quite important aspect in the overall effect of the khat alkaloid. Thus, it has been reported that (-)-cathinone decreases the ability of cats to differentiate between visual stimuli, and that this decrease does not occur when the animals are pre treated with either the serotonin synthesis blocker pchlorphenylalanine or the serotonin receptor antagonist methysergide [14], Furthermore, by using a two-lever drug discrimination procedure it was found that rats trained with the serotonin agonist quipazine were less likely to distinguish between (-)-cathinone and quipazine than between (+)-amphetamine and quipa/ine [15], This observation correlates with results indicating that the affinity of (-)-cathinone for rat fundus serotonin recep tors is four times higher than that of racemic amphet amine [16], It is possible, therefore, that due to higher activity at postsynaptic sites, (-)-cathinone has a gener ally more pronounced effect on serotoninergic neuro transmission than (+)-amphetamine, and it would be of interest to investigate this further. With regard to release from serotonin storage sites, however, (-)-cathinone ap pears to have no greater specificity than (-^-amphet amine.…”

Khat (<b><i>Catha edulis</i></b>) and Obesity: A Scoping Review of Animal and Human Studies

“…In vitro studies, for instance, have shown that cathinone enhances the release of serotonin from the striatum [70,71] and can bind to serotonin receptors [72] . A study by Fleckenstein et al [73] demonstrated serotonin uptake inhibition by cathinone following single or multiple dosing.…”

Distinct single cell signal transduction signatures in leukocyte subsets stimulated with khat extract, amphetamine-like cathinone, cathine or norephedrine

“…Like amphetamine, cathinone induces release of dopamine, serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline from pre-synaptic neuronal terminals, and has further been suggested to inhibit neurotransmitter reuptake [3]. Cathinone, cathine and norephedrine have been shown to act as substrates at the noradrenaline and dopamine transporters, to bind α 2 -adrenergic receptors [9,10], and cathinone has in addition been reported to bind 5-HT receptors [10,11]. The β 1 -adrenergic receptor was suggested to mediate khat-induced increase in systolic blood pressure and pulse rate [12], whereas the α 1 -adrenergic receptor has been implicated in bladder dysfunction following khat chewing [13].…”