Mechanism of Action
Cathinone – an overview. Cathinone has similar CNS stimulatory and sympathomimetic effects characterized by increased blood pressure, heart rate, mydriasis, and hyperthermia similar to amphetamine [88]. All cathinones including natural cathinone and its synthetic derivatives (bath salts) are inhibitors of monoamine transporters, but their selectivity for serotonin receptors, norepinephrine transporter, and dopamine transporters vary substantially.
The mechanism of cathinone on neurotransmission is to trigger presynaptic dopamine release and reduce the reuptake of dopamine which is similar to mechanism by which amphetamine exerts its pharmacological effects. Cathinone although binds to dopamine and serotonin receptors, it has the highest affinity for norepinephrine receptors. Moreover, cathinone has also been shown to induce serotonin release and inhibits its reuptake [89].
Pharmacology and Toxicology
CA are a class of molecules derived from cathinone ((S)-2-amino-1-phenyl-1-propanone), a naturally occurring psychoactive compound present in Catha edulis, a plant commonly known as khat. Khat has been used for centuries in East Africa and the Arabian Peninsula for its psychoactive properties [17]. Cathinone is a beta-ketone amphetamine analog that can be structurally modified to give rise to large number of synthetic compounds (Fig. 21.1).
Cathinone – an overview. In the 1990s, methcathinone was the first reported CA, widely abuse in the United States [18]. While sporadic abuse of methcathinone is still reported, the use of other CA has become epidemic. CA found within “legal high” products mostly include methylone, ethylone, butylone, mephedrone, 4-methylethcathinone (4-MEC), and 3,4-methylenedioxypyrovalerone (MDPV), among hundreds of derivatives available via the internet [19,20].
Among CA derivatives, bupropion is the only cathinone derivative with a reported therapeutic use, with several studies highlighting its beneficial activity in major depressive disorder treatments [21–24], in smoking cessation programs [25], as well as in obesity treatments [26]. In fact, bupropion demonstrated to be useful in modulating psychiatric disorders without the incurrence of some side effects, such as weight gain [27]. On the other hand, all other CA have been strongly associated with abuse for recreational purposes.
In particular, mephedrone and MDPV consumption has been massively reported [28] and an alarming number of intoxications, as well as fatalities, were assessed from case studies [29–31]. Nevertheless, it is clear that CA cause numerous severe health effects, from neurological to hepatic damage, among many others [32–34]. CA follow a path common to many drugs of abuse: a rapid onset of psychostimulant effects, including an increased sense of confidence, libido, and energy [35] followed by unpleasant symptoms such as psychosis, anxiety and paranoia [36], and leading, in some cases, to death [37]. Cathinone – an overview
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