Khat alkaloids

Chewing leaves of the khat shrub is practiced in parts of East Africa and the Arabian peninsula (Kalix 1988 Widler et al. 1994). Some estimate daily use at 5 million portions. Use in the West is less common, but has increased somewhat. More common in the United States has been use of the synthetic drug methcathinone (or "cat"), which is derived from khat alkaloids. Only the fresh khat leaves are pharmacologically active, so for some time use was limited to local areas that grew the plant. However, with air transportation, use has spread with emigrants in Europe and the United States. Because of its pharmacological similarities to amphetamine and its addictive properties, khat has been listed on Schedule I of the United Nations Convention on Psychotropic Substances. 

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. 

Scheme 5. Esterifying acids of the sesquiterpene cores of khat alkaloids. (The numbering indicated is as transferred from the intact alkaloids).

Toennes SW, Kauert GF. Driving nnder the inflnence of khat—alkaloid concentrations and observations in forensic cases. Forensic Sci Int 2004 140(1) 85-90. 

In this chapter, ephedrine and related alkaloids, the khat alkaloids (which are related to the ephedrines), and two other types of alkaloids are described. One of them is the naphthalene-isoquinoline alkaloids, which are described in Section 16.3.These alkaloids might also be classified as alkaloids derived from phenylalanine because they possess an isoquinoline skeleton. However, an extra Cj unit has been joined to the carbon to which the nitrogen is attached, as occurs in the case of ephedrine. Therefore, it is considered that the formation of these alkaloids might involve a biosynthetic pathway not utilizing phenylalanine. The other alkaloids are capsaicin and related alkaloids, which are described in Section 16.4. 

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... 

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

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... 

Crombie L, Crombie WML and Whiting DA (1990) Alkaloids of khat (Catha edulis). The Alkaloids, Chemistry and Pharmacology (ed Brossi A) Vol 39. Academic, San Diego, pp 139-164. 

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. 

Another important source of alkaloids of the ephedrine type is the khat shrub Catha edulis (284), cultivated in certain parts of eastern Africa and southern Arabia. Two major alkaloids in khat are norpseudoephedrine and norephedrine, which occur in a proportion of approximately 4 1 (250). A new alkaloid, (S)-2-aminopropiophenone, has been discovered in fresh leaves of khat and... 

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). 

An alkaloid obtained from catha, the fresh or dried leaves of Catha edulis (Celastraceae). Catha (also known as Abyssinian, African, or Arabian Tea Kat Kath Khat Miraa) is used in northern and eastern Africa as a stimulant, the leaves either being chewed or used as an infusion. 

TLC of Alkaloids from Khat A comparatively simple TLC system can be used for analysis of these drugs, involving separation on silica gel using a mobile phase which causes ion-suppression, and visualizing the chromatogram with nin-hydrin [4]. 

The chromatogram is prepared, developed and visualized by following the same principles as those used for other drug classes. While cathinone is reported to separate from the other alkaloids (essential for the identification of Khat), norpseudoephedrine and norephedrine do not separate in such a system and thus further confirmation of the drug identity is required. 

HPLC of Alkaloids from Khat HPLC can be used to identify the drugs present in this controlled substance, with resolution of cathinone, norpseudoephedrine and norephedrine being achieved on silica gel (as the stationary phase), with a mobile phase consisting of 1,2-dichloroethane/methanol/acetic acid/diethylamine/water (800 200 10 5 5, by volume), employing UV detection at 257 nm [7]. This method has also been used to quantify the drug components present in these samples. However, retention time data were not provided in this paper. 

In early work Stockman (8,9) had obtained an alkaloid preparation from khat which he called cathidine, and mass spectrometric examination of an old preparation led Luftmann and Spiteller (44) to the view that it was a mixture based on a reduction product of the evonine sesquiterpene core esterified with acetic, benzoic, trimethoxybenzoic, nicotinic, and evoninic acids. Ginsburg and colleagues (45) also examined cathidine which they had reisolated from khat and found that it contained at least four compounds. One of these, cathidine D, was studied in some detail and formulated as being either 28 or 29 (45). 

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