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Proconvulsant effect of khat (Catha edulis) in Sprague dawley rats
Journal of Ethnopharmacology 121 (2009) 476–478
Contents lists available at ScienceDirect
Journal of Ethnopharmacology journal homepage: www.elsevier.com/locate/jethpharm
Ethnopharmacological communication
Proconvulsant effect of khat (Catha edulis) in Sprague dawley rats Eren Oyungu a,∗ , Paul G. Kioy b , Nilesh B. Patel b a b
Department of Medical Physiology, Moi University, P.O Box 4606, Eldoret, Kenya Department of Medical Physiology, School of Medicine, University of Nairobi, P.O. Box 30197-00100, Nairobi, Kenya
a r t i c l e
i n f o
Article history: Received 21 February 2008 Received in revised form 22 October 2008 Accepted 30 October 2008 Available online 8 November 2008 Keywords: Khat Rats PTZ seizure threshold Amphetamine Methylphenidate
a b s t r a c t Ethnopharmacological relevance: Catha edulis (khat) is a plant whose fresh young leaves are used by an estimated five million people in eastern Africa and the Arabian Peninsula as a drug of recreation. The fresh leaves and shoots are rich in cathinone, a psychostimulant with effects similar to those of amphetamines. Psychostimulants produce a dose-related excitation of the central nervous system which can lead to seizures and convulsions. However there are no reports on studies of the effect of this herb on brain excitability and seizures. This knowledge is useful for doctors who may prescribe drugs whose side effects include lowering seizure threshold because there could be additive proconvulsant effect among khat users. Aim of the study: to determined whether khat lowers pentylenetetrazole (PTZ) seizure threshold. Methodology: Male Sprague dawley rats were given fresh aqueous khat extract, old aqueous khat extract (3 g/kg bw), methylphenidate or saline and the timed intravenous (PTZ) seizure threshold test was used to study its effect on seizure threshold. Results: Fresh khat (3 g/kg) and methylphenidate (4 mg/kg) lowered PTZ seizure threshold. Conclusion: Khat lowers seizure threshold. © 2008 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Khat refers to the young leaves and twigs of an evergreen shrub (Catha edulis), which is widely consumed in the Arabian Peninsula and Eastern Africa (Kalix, 1984). In 1975 it was estimated that between five and ten million people used khat (Catha edulis) daily (United Nations Document, 1975) and since then the number is likely to have increased. The availability of air transport and refrigerated storage facilities and emigration has contributed to the spread of khat use to other parts of the world where it was not traditionally used, e.g. Europe, United States of America. Depending on the region, khat is known by different names: miraa (Kenya) and qat (Ethiopia). The effects of khat in humans are characterized by moderate central nervous system stimulation resulting in a state of euphoria, increased alertness, excitement, insomnia and anorexia, often accompanied by loquacity or even logorrhea (Kalix, 1987). High consumption can induce hyperactivity that may lead to maniac behavior or a state resembling paranoid–schizophrenia (Al-Harbori, 2005; Alem and Shibre, 1997; Jager and Sireling, 1994). The leaves contain psychoactive agents, cathinone and cathine (dnorpseudoephedrine), which are listed as controlled substances by the United States Drug Enforcement Agency.
∗ Corresponding author. Tel.: +254 722 344312; fax: +254 053 20 33041. E-mail address: [email protected] (E. Oyungu). 0378-8741/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jep.2008.10.037
The molecular structure of cathinone and its effect on the CNS is similar to amphetamine and is considered to be the main active ingredient responsible for the effect of fresh khat on the central nervous system (Szendrei, 1980; Kalix, 1984; Kalix, 1987; Patel, 2000). Cathinone is found predominantly in the fresh khat leaves and over a period of hours to few days is reduced to cathine (Szendrei, 1980; Halket et al., 1995) and has been shown to increase locomotor activity in mice and rats within 30 min after administration (Zelger et al., 1980). Cathine has a stimulatory effect on locomotor activity in rats and mice but with a longer latency (90–120 min). As the effect of khat on the central nervous system is similar to amphetamines, which are known to have proconvulsant activity (O’Brien, 1997), we investigated whether khat would also have an effect on seizure threshold using the pentylenetetrazole (PTZ) test. 2. Materials and methods 2.1. Animals A total of 40 adult male Sprague dawley rats (200–500 g) were used. They were obtained from the Department of Biochemistry, College of Health Sciences, University of Nairobi and were housed in rat cages in the animal house, Department of Medical Physiology. The cages were cleaned and bedding changed three times per week. The rats were kept on a twelve hour light/dark cycle and fed on standard rodent pellets and water ad libitum. Each rat was habituated to
E. Oyungu et al. / Journal of Ethnopharmacology 121 (2009) 476–478
477
the experimental set up by transferring it to the observation chamber (30 cm × 30 cm × 30 cm plexiglass box) for 30 min daily for five days before the start of the experiments. The care of animals conformed to the guidelines for the care and use of laboratory animals of the US National Research Council (1996). 2.2. Preparation of aqueous extract of khat Fresh khat, less than 24 h old, was purchased on the day of the experiment from one retailer who received daily supply from Meru, Kenya. A stock solution of fresh khat was prepared on the day of experiment by blending 300 g of fresh khat in 50 ml of normal saline to give a solution of khat extract equivalent to 6 g/ml. The mixture was then filtered (Whatman number 1 filter paper, Whatman Plc., USA) and the decoction used in the experiments. Old khat was prepared by leaving stock solution of old khat at room temperature for three days for the cathinone to reduce to cathine (Szendrei, 1980) 2.3. Methylphenidate Methylphenidate (Norvatis AG. Switzerland), an amphetamine analog and established central nervous system stimulant, was used for comparison. The tablets were ground into powder and dissolved in normal saline to make stock solution of 5 mg/ml.
Fig. 1. PTZ seizure threshold in rats treated with normal saline, old khat, fresh khat or methylphenidate. Pentylenetetrazole (PTZ) required to induce seizures in rats treated with either fresh khat (3 g/kg bw), old khat (3 g/kg bw), methylphenidate (4 mg/kg bw) or saline. n = 10. *p < 0.01.
comparisons was used to test for significant difference between test groups and the saline group. p < 0.05 was considered significant. Results are presented as mean ± S.D.
2.4. Pentylenetetrazole (PTZ) 3. Results Pentylenetetrazole (Aldrich Chemicals) was prepared by dissolving 100 mg of the powder in 20 ml of water to obtain a concentration of 5 mg/ml. 2.5. Proconvulsant studies The timed intravenous PTZ seizure threshold test as described by Polack and Shen (1985) for quantitating anticonvulsant effect of drugs was used in this study. Rats were randomly assigned to one of the following treatment groups (n = 10): (a) fresh khat (3 g/kg bw), (b) old khat (3 g/kg bw), (c) methylphenidate (4 mg/kg bw) and (d) normal saline. The khat and methylphenidate doses selected were based on doses that increase locomotor activity without inducing behavioural seizures as found in dose response curve studies reported from our laboratory earlier (Oyungu et al., 2007). The dose was also selected in such a way that it simulated the amount of khat consumed by human beings in one day for recreational purposes based on case control study done in Somalia (Odenwald et al., 2005). For cannulation, each rat was anaesthetized with ketamine (100 mg/kg i.p.) and a 2 cm vertical incision made on the medial surface of one hind limb to expose the femoral vein which was catheterized with a gauge 24 cannula (Mediflon G24) and secured with suture. The rats were allowed 24 h to recover from anaesthesia and the surgical procedure. On the experiment day, each rat was given the experimental drug through a gastric tube in a volume of 5 ml and then placed in the observation chamber. After 45 min, a PTZ drip (Soluset, Braun® ) was connected and started at a rate of 30 drops per minute and stopped when a general clonus (clonus of all the four limbs) with transient loss of righting reflex occurred. The dose of PTZ (mg/kg) that induced general clonus was calculated and recorded as an index of seizure threshold.
The dose of pentylenetetrazole that induced seizures in rats pretreated with fresh khat (3 g/kg bw), old khat (3 g/kg bw), methylphenidate (4 mg/kg bw) or normal saline was 18.7 ± 5.6, 45.6 ± 17.6, 24.7 ± 8.9 and 55.4 ± 16.2 mg/kg, respectively (Fig. 1). There was a significant difference in the amount of intravenous PTZ needed to induce clonic seizures in these four groups (F(3,36) = 17.54, p < 0.01). Post hoc analysis showed a significant decrease in the PTZ threshold with fresh khat and methylphenidate treatment compared to old khat treatment or saline (p < 0.01). There was no significant difference between old khat and saline treated rats. 4. Discussion and conclusion Seizures in vertebrates can be induced by electrical or chemical stimuli. Chemical stimuli that induce seizures may decrease inhibitory or enhance excitatory neuronal activity in the brain. Amphetamines have in vivo epileptogenic property which could be related to their ability to increase extracellular biogenic amines levels that interact with both excitatory and inhibitory neuronal systems (Zagnone and Albano, 2002). In this study, khat, which has been described as natural amphetamine, given at doses similar to those used by humans for recreation purpose (Odenwald et al., 2005), was found to lower PTZ seizure threshold as did methylphenidate, an amphetamine analogue. Increase in incidence of seizures has been found in patients who concomitantly use amphetamine and other drugs with proconvulsant activity like some antidepressants (O’Brien, 1997; Feeney and Klykylo, 1997). Although there are no published reports of seizures induced by khat, khat users may be at risk of seizures when they are treated with drugs that may have proconvulsant potential. Acknowledgement
2.6. Analysis One way Analysis of Variance (ANOVA) was used to find statistical difference between groups. Bonferoni’s correction for multiple
We wish to acknowledge Messres. C. Wainaina, E. Ndungu, C. Kinyungu and C. Owuor for their technical assistance. This work received financial support from MHO Moi University Project.
478
E. Oyungu et al. / Journal of Ethnopharmacology 121 (2009) 476–478
References Al-Harbori, M., 2005. The potential adverse effects of habitual use of Catha edulis (khat). Expert Opinion on Drug Safety 4, 1145–1154. Alem, A., Shibre, T., 1997. Khat induced psychosis and its medico-legal implications: a case report. Ethiopian Medical Journal 35, 137–139. Feeney, D.J., Klykylo, W.M., 1997. Medication induced seizures [letter]. Journal of American Academy Child Adolescent Psychiatry 36, 1018–1019. Guide for the Care and Use of Laboratory Animals. Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council. National Academy Press, Washington DC, 1996. Halket, J.M., Karasu, Z., Murray–Lyon, I.U., 1995. Plasma cathinone levels following chewing khat leaves (Catha edulis Forsk). Journal of Ethnopharmacology 49, 111–113. Jager, A.D., Sireling, L., 1994. Natural history of khat psychosis. Australian and New Zealand Journal of Psychiatry 28, 331–332. Kalix, P., 1984. Recent advances in khat research. Alcohol and Alcoholism 19, 319–323. Kalix, P., 1987. Khat: Scientific knowledge and policy issues. British Journal of Addiction 82, 47–53. O’Brien, C.P., 1997. Drug addiction and drug abuse. In: Goodman, J.G., Gilman, A.G. (Eds.), The Pharmacological Basis of Therapeutics, 9th ed. McGraw-Hill, New York.
Odenwald, M., Neuner, F., Schauer, M., et al., 2005. Khat use as a risk factor for psychotic disorders. A cross-sectional and case control study in Somalia. BMC Medicine 3, 5. Oyungu, E., Kioy, P.G., Patel, N.B., 2007. Effect of Catha edulis on behavior and its potential to induce seizures in Sprague dawley rats. East African Medical Journal 84, 219–225. Patel, N.B., 2000. Mechanism of action of cathinone, the active ingredient of khat. East African Medical Journal 77, 299–332. Polack, G.M., Shen, D.D., 1985. A timed intravenous pentylenetetrazol infusion seizure model for quantitating the anticonvulsant effect of valproic acid in rats. Journal of Pharmacological Methods 13, 135–146. Szendrei, K., 1980. The chemistry of khat. Bulletin on Narcotics 32, 5–36. United Nations Document. 1975. Etude sur la composition chimique du khat; Recherches sur la fraction phenylalkylamine. MNAR/11/1975. Zagnone, P.G., Albano, C., 2002. Psychostimulants and Epilepsy. Epilepsia 43, 28. Zelger, J.L., Schorno, H.X., Carlini, E., 1980. Behavioral effects of cathinone, an amine obtained from Catha edulis Forsk: Comparison with amphetamine, norpseudoephedrine, apormorphine and nomifensine. Bulletin on Narcotics. 32, 67–81.
Contents lists available at ScienceDirect
Journal of Ethnopharmacology journal homepage: www.elsevier.com/locate/jethpharm
Ethnopharmacological communication
Proconvulsant effect of khat (Catha edulis) in Sprague dawley rats Eren Oyungu a,∗ , Paul G. Kioy b , Nilesh B. Patel b a b
Department of Medical Physiology, Moi University, P.O Box 4606, Eldoret, Kenya Department of Medical Physiology, School of Medicine, University of Nairobi, P.O. Box 30197-00100, Nairobi, Kenya
a r t i c l e
i n f o
Article history: Received 21 February 2008 Received in revised form 22 October 2008 Accepted 30 October 2008 Available online 8 November 2008 Keywords: Khat Rats PTZ seizure threshold Amphetamine Methylphenidate
a b s t r a c t Ethnopharmacological relevance: Catha edulis (khat) is a plant whose fresh young leaves are used by an estimated five million people in eastern Africa and the Arabian Peninsula as a drug of recreation. The fresh leaves and shoots are rich in cathinone, a psychostimulant with effects similar to those of amphetamines. Psychostimulants produce a dose-related excitation of the central nervous system which can lead to seizures and convulsions. However there are no reports on studies of the effect of this herb on brain excitability and seizures. This knowledge is useful for doctors who may prescribe drugs whose side effects include lowering seizure threshold because there could be additive proconvulsant effect among khat users. Aim of the study: to determined whether khat lowers pentylenetetrazole (PTZ) seizure threshold. Methodology: Male Sprague dawley rats were given fresh aqueous khat extract, old aqueous khat extract (3 g/kg bw), methylphenidate or saline and the timed intravenous (PTZ) seizure threshold test was used to study its effect on seizure threshold. Results: Fresh khat (3 g/kg) and methylphenidate (4 mg/kg) lowered PTZ seizure threshold. Conclusion: Khat lowers seizure threshold. © 2008 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Khat refers to the young leaves and twigs of an evergreen shrub (Catha edulis), which is widely consumed in the Arabian Peninsula and Eastern Africa (Kalix, 1984). In 1975 it was estimated that between five and ten million people used khat (Catha edulis) daily (United Nations Document, 1975) and since then the number is likely to have increased. The availability of air transport and refrigerated storage facilities and emigration has contributed to the spread of khat use to other parts of the world where it was not traditionally used, e.g. Europe, United States of America. Depending on the region, khat is known by different names: miraa (Kenya) and qat (Ethiopia). The effects of khat in humans are characterized by moderate central nervous system stimulation resulting in a state of euphoria, increased alertness, excitement, insomnia and anorexia, often accompanied by loquacity or even logorrhea (Kalix, 1987). High consumption can induce hyperactivity that may lead to maniac behavior or a state resembling paranoid–schizophrenia (Al-Harbori, 2005; Alem and Shibre, 1997; Jager and Sireling, 1994). The leaves contain psychoactive agents, cathinone and cathine (dnorpseudoephedrine), which are listed as controlled substances by the United States Drug Enforcement Agency.
∗ Corresponding author. Tel.: +254 722 344312; fax: +254 053 20 33041. E-mail address: [email protected] (E. Oyungu). 0378-8741/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jep.2008.10.037
The molecular structure of cathinone and its effect on the CNS is similar to amphetamine and is considered to be the main active ingredient responsible for the effect of fresh khat on the central nervous system (Szendrei, 1980; Kalix, 1984; Kalix, 1987; Patel, 2000). Cathinone is found predominantly in the fresh khat leaves and over a period of hours to few days is reduced to cathine (Szendrei, 1980; Halket et al., 1995) and has been shown to increase locomotor activity in mice and rats within 30 min after administration (Zelger et al., 1980). Cathine has a stimulatory effect on locomotor activity in rats and mice but with a longer latency (90–120 min). As the effect of khat on the central nervous system is similar to amphetamines, which are known to have proconvulsant activity (O’Brien, 1997), we investigated whether khat would also have an effect on seizure threshold using the pentylenetetrazole (PTZ) test. 2. Materials and methods 2.1. Animals A total of 40 adult male Sprague dawley rats (200–500 g) were used. They were obtained from the Department of Biochemistry, College of Health Sciences, University of Nairobi and were housed in rat cages in the animal house, Department of Medical Physiology. The cages were cleaned and bedding changed three times per week. The rats were kept on a twelve hour light/dark cycle and fed on standard rodent pellets and water ad libitum. Each rat was habituated to
E. Oyungu et al. / Journal of Ethnopharmacology 121 (2009) 476–478
477
the experimental set up by transferring it to the observation chamber (30 cm × 30 cm × 30 cm plexiglass box) for 30 min daily for five days before the start of the experiments. The care of animals conformed to the guidelines for the care and use of laboratory animals of the US National Research Council (1996). 2.2. Preparation of aqueous extract of khat Fresh khat, less than 24 h old, was purchased on the day of the experiment from one retailer who received daily supply from Meru, Kenya. A stock solution of fresh khat was prepared on the day of experiment by blending 300 g of fresh khat in 50 ml of normal saline to give a solution of khat extract equivalent to 6 g/ml. The mixture was then filtered (Whatman number 1 filter paper, Whatman Plc., USA) and the decoction used in the experiments. Old khat was prepared by leaving stock solution of old khat at room temperature for three days for the cathinone to reduce to cathine (Szendrei, 1980) 2.3. Methylphenidate Methylphenidate (Norvatis AG. Switzerland), an amphetamine analog and established central nervous system stimulant, was used for comparison. The tablets were ground into powder and dissolved in normal saline to make stock solution of 5 mg/ml.
Fig. 1. PTZ seizure threshold in rats treated with normal saline, old khat, fresh khat or methylphenidate. Pentylenetetrazole (PTZ) required to induce seizures in rats treated with either fresh khat (3 g/kg bw), old khat (3 g/kg bw), methylphenidate (4 mg/kg bw) or saline. n = 10. *p < 0.01.
comparisons was used to test for significant difference between test groups and the saline group. p < 0.05 was considered significant. Results are presented as mean ± S.D.
2.4. Pentylenetetrazole (PTZ) 3. Results Pentylenetetrazole (Aldrich Chemicals) was prepared by dissolving 100 mg of the powder in 20 ml of water to obtain a concentration of 5 mg/ml. 2.5. Proconvulsant studies The timed intravenous PTZ seizure threshold test as described by Polack and Shen (1985) for quantitating anticonvulsant effect of drugs was used in this study. Rats were randomly assigned to one of the following treatment groups (n = 10): (a) fresh khat (3 g/kg bw), (b) old khat (3 g/kg bw), (c) methylphenidate (4 mg/kg bw) and (d) normal saline. The khat and methylphenidate doses selected were based on doses that increase locomotor activity without inducing behavioural seizures as found in dose response curve studies reported from our laboratory earlier (Oyungu et al., 2007). The dose was also selected in such a way that it simulated the amount of khat consumed by human beings in one day for recreational purposes based on case control study done in Somalia (Odenwald et al., 2005). For cannulation, each rat was anaesthetized with ketamine (100 mg/kg i.p.) and a 2 cm vertical incision made on the medial surface of one hind limb to expose the femoral vein which was catheterized with a gauge 24 cannula (Mediflon G24) and secured with suture. The rats were allowed 24 h to recover from anaesthesia and the surgical procedure. On the experiment day, each rat was given the experimental drug through a gastric tube in a volume of 5 ml and then placed in the observation chamber. After 45 min, a PTZ drip (Soluset, Braun® ) was connected and started at a rate of 30 drops per minute and stopped when a general clonus (clonus of all the four limbs) with transient loss of righting reflex occurred. The dose of PTZ (mg/kg) that induced general clonus was calculated and recorded as an index of seizure threshold.
The dose of pentylenetetrazole that induced seizures in rats pretreated with fresh khat (3 g/kg bw), old khat (3 g/kg bw), methylphenidate (4 mg/kg bw) or normal saline was 18.7 ± 5.6, 45.6 ± 17.6, 24.7 ± 8.9 and 55.4 ± 16.2 mg/kg, respectively (Fig. 1). There was a significant difference in the amount of intravenous PTZ needed to induce clonic seizures in these four groups (F(3,36) = 17.54, p < 0.01). Post hoc analysis showed a significant decrease in the PTZ threshold with fresh khat and methylphenidate treatment compared to old khat treatment or saline (p < 0.01). There was no significant difference between old khat and saline treated rats. 4. Discussion and conclusion Seizures in vertebrates can be induced by electrical or chemical stimuli. Chemical stimuli that induce seizures may decrease inhibitory or enhance excitatory neuronal activity in the brain. Amphetamines have in vivo epileptogenic property which could be related to their ability to increase extracellular biogenic amines levels that interact with both excitatory and inhibitory neuronal systems (Zagnone and Albano, 2002). In this study, khat, which has been described as natural amphetamine, given at doses similar to those used by humans for recreation purpose (Odenwald et al., 2005), was found to lower PTZ seizure threshold as did methylphenidate, an amphetamine analogue. Increase in incidence of seizures has been found in patients who concomitantly use amphetamine and other drugs with proconvulsant activity like some antidepressants (O’Brien, 1997; Feeney and Klykylo, 1997). Although there are no published reports of seizures induced by khat, khat users may be at risk of seizures when they are treated with drugs that may have proconvulsant potential. Acknowledgement
2.6. Analysis One way Analysis of Variance (ANOVA) was used to find statistical difference between groups. Bonferoni’s correction for multiple
We wish to acknowledge Messres. C. Wainaina, E. Ndungu, C. Kinyungu and C. Owuor for their technical assistance. This work received financial support from MHO Moi University Project.
478
E. Oyungu et al. / Journal of Ethnopharmacology 121 (2009) 476–478
References Al-Harbori, M., 2005. The potential adverse effects of habitual use of Catha edulis (khat). Expert Opinion on Drug Safety 4, 1145–1154. Alem, A., Shibre, T., 1997. Khat induced psychosis and its medico-legal implications: a case report. Ethiopian Medical Journal 35, 137–139. Feeney, D.J., Klykylo, W.M., 1997. Medication induced seizures [letter]. Journal of American Academy Child Adolescent Psychiatry 36, 1018–1019. Guide for the Care and Use of Laboratory Animals. Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council. National Academy Press, Washington DC, 1996. Halket, J.M., Karasu, Z., Murray–Lyon, I.U., 1995. Plasma cathinone levels following chewing khat leaves (Catha edulis Forsk). Journal of Ethnopharmacology 49, 111–113. Jager, A.D., Sireling, L., 1994. Natural history of khat psychosis. Australian and New Zealand Journal of Psychiatry 28, 331–332. Kalix, P., 1984. Recent advances in khat research. Alcohol and Alcoholism 19, 319–323. Kalix, P., 1987. Khat: Scientific knowledge and policy issues. British Journal of Addiction 82, 47–53. O’Brien, C.P., 1997. Drug addiction and drug abuse. In: Goodman, J.G., Gilman, A.G. (Eds.), The Pharmacological Basis of Therapeutics, 9th ed. McGraw-Hill, New York.
Odenwald, M., Neuner, F., Schauer, M., et al., 2005. Khat use as a risk factor for psychotic disorders. A cross-sectional and case control study in Somalia. BMC Medicine 3, 5. Oyungu, E., Kioy, P.G., Patel, N.B., 2007. Effect of Catha edulis on behavior and its potential to induce seizures in Sprague dawley rats. East African Medical Journal 84, 219–225. Patel, N.B., 2000. Mechanism of action of cathinone, the active ingredient of khat. East African Medical Journal 77, 299–332. Polack, G.M., Shen, D.D., 1985. A timed intravenous pentylenetetrazol infusion seizure model for quantitating the anticonvulsant effect of valproic acid in rats. Journal of Pharmacological Methods 13, 135–146. Szendrei, K., 1980. The chemistry of khat. Bulletin on Narcotics 32, 5–36. United Nations Document. 1975. Etude sur la composition chimique du khat; Recherches sur la fraction phenylalkylamine. MNAR/11/1975. Zagnone, P.G., Albano, C., 2002. Psychostimulants and Epilepsy. Epilepsia 43, 28. Zelger, J.L., Schorno, H.X., Carlini, E., 1980. Behavioral effects of cathinone, an amine obtained from Catha edulis Forsk: Comparison with amphetamine, norpseudoephedrine, apormorphine and nomifensine. Bulletin on Narcotics. 32, 67–81.