Gastric antiulcer and cytoprotective effects of cathinone, a psychoactive alkaloid of khat (Catha edulis forsk.) and amphetamine in rats

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GASTRIC ANTIULCER AND CYTOPROTECTIVE EFFECTS OF CATHINONE, A PSYCHOACTIVE ALKALOID OF KHAT (CRTHA E2)ITLIS FORSK. ) AND AMPHETAMINE IN RATS. O.A. Ai-Shabanah, N.M. Ai-Gharably, M.W. Islam & M.M. Al-Narbi, Dept. of Pharmacology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. (-)-Cathinone, chemically known as (-)-a-aminopropiophenone is an active constituent of khat (Catha edulis Forsk.). The leaves of khat plant are chewed customarily in Southern Arabia and Eastern Africa, to attain a state of euphoria and stimulation. WHO classified khat as drug of abuse. U.N. Narcotic Laboratory considered cathinone as natural amphetamine, due to its close similarity with that of amphetamine. The controversial observations on the gastrointestinal effects of khat chewing prompted us to study the effect of cathinone on experimentally induced gastric ulcers in rats, and compare it with that of amphetamine. These data showed that oral administration of cathinone (I0 and 30 mg/kg) and amphetamine (i and 3 mg/kg) inhibited the formation of gastric lesions induced by NSAIDs (aspirin, indomethacin, phenylbutazone) and cytodestructive agents including 0.6M Hcl, 0.2M NaON, 80% ethanol and 25% Nacl. The antiulcer effect of cathinone and amphetamine was accompanied by a significant antisecretory effect. Methods: Wistar albino rats of either sex (200-250 g), aged approximately five weeks, were obtained from the Animal Care Centre, College of Pharmacy, King Saud University, Riyadh. They were acclimatised to a room temperature of 23 ± I °C and a 12h light-dark cycle for at least 3-4 days before experiments and fed on laboratory chow diet and tap water ad libitum. The preparation of solutions of test and ulcerogenic drugs and the details of the methods have been discussed in our previous work (i). (-)-Cathinone was synthesised according to the method of AI-Meshal et al., (2). (+) Amphetamine Hcl (Merck, Sharp and Dohme, U.S.A.), Aspirin (Buyer-Pharma Sens Cedex, France) and indomethacin and phenylbutazone (Ciba-Geigy, Switzerland) were used. Results and discussion: Cathinone in doses of 0.5-2mg/kg and amphetamine in doses of 0.I mg/kg produced haemorrhagia in the glandular segment of the stomach. The spots of the blood effused on the tissues showed no resistance on wiping with saline. On the other hand, treatment with higher doses did not produce such effects. The mechanism by which small doses of cathinone and amphetamine produced haemorrhagia is not clear yet, however, sympathetic stimulants have been shown to produce gastric haemorragia in lower doses (3). Cathinone in dose of 10 and 30 mg/kg showed significant (P < 0.5) doserdependent decrease in the intensity of gastric mucosal damage induced by aspirin, indomethacin or phenylbutazone at 1 and 6 h after treatment. These significant reductions in gastric ulcers have been also observed following pretreamtnt with amphetamine (1 and 3 mg/kg). The cytoprotective effects of cathinone and amaphetamine against different necotising agents have been investigated. Both cathinone and amphetamine produced a significant dose-dependent cytoprotective effect against all necrotising agents used (0.6 MHC!; 0.2 M NaoH; 80% ethanol; 25% NaCI). However, in the animals treated with amphetamine (I mg/kg) against 0.6 MHCI and cathinone (10 mg/kg) against 25% NaCl at 1 and 6 h, the protective effects of the drugs were not statistically significant. These antiulcer effects are associated with antisecretory effects. Pylorus ligation for 1 h and 6 h resulted in the production of gastric ulceration, mainly in the foremost stomach, accumulation of gastric secretions and an increase in the titrable acidity and total acid output. The animal given cathinone or amphetamine showed significant reductions in ulcer index, secretory volume and total acid output (Table I). However, cathinone appeared to be a less potent antisecretory agent than amphetamine.

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These results show that the oral administration of cathinone and amphetamine inhibited the formation of gastric ulcers in rats induced by different ulcerogenic models. The ability of cathinone and amphetamine to produce a significant reduction in the intensity of gastric mucosal damage confirms their potential anti-ulcer activity. These findings are in agreement with earlier report on the ulcer inhibiting effects of crude khat (4). Also, the anti-ulcer and cytoprotective effects of cathinone and amphetamine observed in the present study further support the view that (-)-cathinone is an amphetamine-like compound. However, the mechanism by which cathinone and amphetamine produced their anti-ulcer effect still need more investigation. REFERENCES:

i. 2. 3. 4.

O.A. Al-Shabanah, M.W. Islam, N.M. AI-Gharably and M.M. AI-Harbi (1993) Research Communications in Substances of Abuse. 14(1) 81-94. I.A. Ai-Meshal, K. Ai-Rashood, M. Nasir, et al., (1987) J. Nat. Prod. 50, 1138-1140. K. Sazabo (1976). In: Mozsik, Gy. and Javer, T. (eds), Progress in Peptic Ulcer, pp. 443-564, Hungary. P. Kalix (1990) Pharmac. Ther., 48, 397-416.