Cathinone

In contrast to what was observed for DOM-like activity, N-monomethylation of AMPH-like agents does not decrease their AMPH-like character. Meth-AMPH (i.e., N-monomethylamphetamine) is slightly more potent than amphetamine likewise, methcathinone (N-monomethylcathinone) is twice as potent as cathinone. N-methylation of DOM-like agents does not convert... 

Ephedrine, for example, produces weak AMPH-like activity (Huang and Ho 1974b). (+)Norpseudoephedrine (cathine) also produces AMPH-like stimulus effects. The oxidized analogs of norephedrine and ephedrine, cathinone and methcathinone, respectively, however, are potent AMPH-like agents (table 2). 

Both optical isomers of AMPH are aetive (Seheehter 1978). In general, for the few isomeric pairs that have been examined, the S isomers of AMPH-like agents are slightly more potent than the raeemates and about 3 times more potent than the R isomers (Young and Glennon 1986). Y(-i-)AMPH, for example, is 3 times more potent than R(-)AMPH (table 2) 5 (-)cathinone is 2.5 times more potent than raeemie eathiione, but (unexpectedly) is nearly 15 times more potent than R(+)cathinone. 

Wagner, G.C. Preston, K. Ricaurte, G.A. Schuster, C.R. and Seiden, L.S. Neurochemical similarities between 4/-cathinone and [Pg.159]

Patel NB. Mechanism of action of cathinone the active ingredient of khat (Catha... 

Cathinone An amphetamine derivative found in khat extracted from Catha edulis growing in the Horn of Africa, where it is widely used as a recreational stimulant. 

Khat (Qat) The Horn of Africa plant Catha edulis containing the amphetamine-like drugs, cathine and cathinone (norpseudoephedrine). 

There are more than 40 alkaloids, glycosides, tannins, and terpenoids in khat (Elmi 1983). Two phenylalkylamines, namely, cathine (norpseudoephedrine) and cathinone [S(-)-alpha-aminopropiophenone] well account for the CNS stimulant effects (Kalix 1988) (figure 4.17). The... 

When khat is chewed, absorption of cathinone is slow, with maximal plasma concentrations occurring at approximately 2 hours (Widler et al. 1994 Halket et al. 1995). The terminal elimination half-life is approximately 4.3 hours. Similar effects are achieved with orally administered pure cathinone. Cathinone is the keto-analog of cathine and because it is more lipophilic it penetrates the blood-brain barrier more easily. 

The plasma half-life of cathinone is 1.5 hours. The primary metabolites are norpseudoephedrine, norephedrine, 3,6-dimethyl-2,5-diphenyl-pyrazine, and l-phenyl-l,2-propanedione (Szendrei 1980 Brenneisen etal. 1986 Guantai and Maitai 1983). However, norpseudoephedrine and norephedrine also originate directly from the leaves, as well as being metabolic products (Widler et al. 1994). Maximal plasma concentrations of norephedrine and norpseudoephedrine are reached at about 3.3 and 3.1 hours, respectively. These two drugs have a much longer duration of action than cathinone, where terminal half-lives could not be calculated after 10 hours. 

Animal drug discrimination paradigms show cross-tolerance between cathinone, cathine, and amphetamine (Schechter 1990). S(-i-)methcathi-... 

Khat produces effects similar to those of other monoamine stimulants, (i.e., increases in mental stimulation, physical endurance, elevated mood) (Widler etal. 1994 Kalix 1994 Brenneisen etal. 1990). Stimulus generalization occurs between cathinone, amphetamine, and cocaine, suggesting similar subjective effects (Huang and Wilson 1986). Similar to other monoamine stimulants, cathinone causes dose-dependent reductions in eating and body weight (Islam et al. 1990 Zelger and Carlini 1980). Oral cathinone increases sexual arousal in rats, but does not affect erectile or ejaculatory responses (Taha et al. 1995). 

Khat produces sympathomimetic effects, increasing heart rate and blood pressure. When khat is chewed, the increases are gradual, maximizing at about 2 hours and lasting for 4 hours. However, tolerance develops to blood pressure and heart rate effects in habitual users. Mydriasis and increases in respiration also occur. Cathinone induces thermogenesis in brown adipose tissue, which is mediated by jS-adrenergic receptors (Tariq et al. 1989). 

Cathinone and norpseudoephedrine have antagonist effects at the neuromuscular junction (Guantai et al. 1987). This is likely a direct blocking effect, independent of cholinergic and adrenergic innervation. However, motor effects are not reported at doses commonly used. 

The similarities between cathinone and amphetamine raises the possibility of abuse potential (Kalix 1994). Amphetamine and cathinone both appear to produce their stimulus-discrimination effects through the dopamine system (Kalix and Glennon 1986). 

Animals self-administer cathinone in a pattern common to abuses of monoamine stimulants such as cocaine (Woolverton and Johanson 1984). Cathinone can induce a conditioned place preference in rats (Schechter 1991). Withdrawal symptoms of khat include lethargy, depression, nightmares, and mild tremor (Kalix 1994). /V-methylated cathinone (methcathinone) is more potent, and has become available on the illegal market. It was subsequently scheduled as a controlled substance (Glennon et al. 1995). 

Use of cathinone in the form of chewing khat may have some features that limit its addictiveness (Kalix 1994). The large bulk of the material and the effort required to chew khat limits the amount that can be ingested in a given time. Absorption in this manner is slow and gradual. 

As would be expected, khat overuse produces symptoms similar to those of other monoamine stimulants, such as cocaine or amphetamine, including signs of sympathetic overarousal. In the extreme this can involve a toxic psychosis. Disorders more frequently associated with chronic khat use in males are headaches, anorexia, insomnia, constipation, and respiratory illnesses (Kennedy et al. 1983). Females report higher incidences of acute gastritis, jaundice, bronchitis and hepatic diseases. Also, cathinone has toxic reproductive effects in humans and experimental animals (Islam et al. 1990). It decreases sperm count and motility, and increases the number of abnormal sperm cells. It also decreases plasma testosterone in rats. 

Brenneisen R, Fisch FiU, Koeibing U, Geisshtisier S, Kaiix P. (1990). Amphetamine-like effects in humans of the khat aikaioid cathinone. BrJ Clin Pharmacol. 30(6) 825-28. 

Halket JM, Karasu Z, Murray-Lyon IM. (1995). Plasma cathinone levels following chewing khat leaves (Catha edulis Forsk.). J Ethnopharmacol. 49(2) 111-13. 

Huang D, Wilson MC. (1986). Comparative discriminative stimulus properties of dl-cathinone, d-amphetamine, and cocaine in rats. Pharmacol Biochem Behav. 24(2) 205-10. 

Islam MW, Tariq M, Ageel AM, el-Feraly FS, al-Meshal lA, Ashraf I. (1990). An evaluation of the male reproductive toxicity of cathinone. Toxicology. 60(3) 223-34. 

Kalix P. (1981). Cathinone, an alkaloid from khat leaves with an amphetamine-like releasing effect. Psychopharmacology (Berlin). 74(3) 269-70. 

Kalix P. (1982). The amphetamine-like releasing effect of the alkaloid (-)cathinone on rat nucleus accumbens and rabbit caudate nucleus. Prog Neuropsychopharmacol Biol Psychiatry. 6(1) 43-49. Kalix P. (1983). A comparison of the catecholamine releasing effect of the khat alkaloids (-)-cathinone and (+)-norpseudoephedrine. Drug Alcohol Depend. 11(3-4) 395-401. 

Kalix P. (1984). Effect of the alkaloid (-)-cathinone on the release of radioactivity from rat striatal tissue prelabelled with 3H-serotonin. Neuropsychobiology. 12(2-3) 127-29. 

Kalix P. (1992). Cathinone, a natural amphetamine. Pharmacol Toxicol. 70(2) 77-86. 

Kalix P, Glennon RA. (1986). Further evidence for an amphetamine-like mechanism of action of the alkaloid cathinone. Biochem Pharmacol. 35(18) 3015-19. 

Mereu GP, Pacitti C, Argiolas A. (1983). Effect of (-)-cathinone, a khat leaf constituent, on dopaminergic firing and dopamine metabolism in the rat brain. Life Sci. 32(12) 1383-89. 

Pehek EA, Schechter MD, Yamamoto BK. (1990). Effects of cathinone and amphetamine on the neurochemistry of dopamine in vivo. Neuropharmacology. 29(12) 1171-76. 

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