Khat Cathinone

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. 

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). 

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. 

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. 

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. 

Taha SA, Ageel AM, Islam MW, GInawl OT. (1995). Effect of (-)-cathinone, a psychoactive alkaloid from khat (Catha edulis Forsk.) and caffeine on sexual behaviour in rats. Pharmacol Res. 31(5) 299-303. 

Khat Catha edulis Leaves Alkaloids cathinone, cathine Chewed, tea Stimulant Yemenis, Ethiopians, Somalis etc. East Arabia, East Africa, Madagascar... 

Chiral protoalkaloids, such as cathinone (55), a psychotropic constituent of Catha edulis Forssk. (khat), have provided probes for studying the mechanistic properties of biogenic amine transporters, and afforded information regarding the effect of stereochemistry at the transportation level of these nitrogenous compounds. ... 

After chewing khat leaves, it can take up to two hours to achieve peak levels of cathinone. The half-life is about 4.5 hours. 

Cathinone is metabolized to norephedrine and norpseudo-ephedrine. Cathinone is found in breast milk. Babies of mothers who used khat have low birth weights. Methcathinone acts like methamphetamine, and effects last four to six hours. 

Khat Catha edulis Ephedrine, cathinone Adrenergic Norepinephrine, epinephrine... 

Khat is found in an African plant, Catha edulis, which contains cathinone and cathine (also known as d-norisoephedrine). The habit of chewing khat to produce a mild arousal probably... 

Although the Catha edulis plant contains a number of chemicals, vitamins, and minerals, its main active ingredient is cathinone, an alkaloid with a chemical structure similar to ephedrine and d-amphetamine. Like amphetamine, it increases the levels of dopamine in the brain and acts as a mild stimulant. For this reason, khat is sometimes referred to as a natural amphetamine. 

Cathinone and cathine are controlled under the United Nations Convention on Psychotropic Substances. In the United States, Canada, Switzerland, Scandinavia, and most of the Middle East, excluding Yemen, the leaf itself is banned. The khat plant is not controlled under domestic law in the United Kingdom. 

Nevertheless, law enforcement efforts directed against khat use in the United States have been minimal as there is some doubt about whether khat will ever become as popular a street drug as marijuana, crack cocaine, and other drugs. However, illegal laboratories have been discovered manufacturing a synthetic form or khat s most active ingredient (cathinone), which is called methcathinone and known on the street as cat. ... 

The fresh leaves of the khat shrub (Catha edulis) are chewed by several millions of people in East Africa and the Arabian peninsula for their euphoric and stimulating properties (284). The rather newly discovered alkaloid cathinone [(S)-a-aminopropiophenone] is responsible for the stimulating properties of khat (284). It has been shown that cathinone induces release at physiological catecholamine storage sites in a manner similar to that of amphetamine. Further results suggest that cathinone and amphetamine produce their stimulant effects via the same dopaminergic mechanism (599). The more recently discovered khat constituents merucathinone, merucathine, and pseudomerucathine were found to have only weak dopamine-releasing effects and were therefore considered unlikely to play an important role in the stimulatory actions of khat leaves (414). 

Neuromessenger Releasers. Normal CNS functioning could be disrupted by evoking premature or continued release of neuromessengers from presynaptic stores. Although D(+)-amphetamine, a well-known psychostimulant and appetite depressant, does not occur in plants, a closely-related substance, DL-cathinone, does occur. It is found in the leaves of the khat shrub, Catha edulis, which grows in East Africa and in the Arab peninsula. Cathinone evokes the release of norepinephrine from central and peripheral presynaptic stores and has cardiovascular and appetite depressing effects similar to D-amphetamine (23). 

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