Quantities of plants powder and distilled water, and part of the plant used to prepare the decoctions. i.p. (intraperitoneal), p.o. (per os).
1. Introduction
Epilepsy is a disease that affects about 40 million people worldwide (Njamshi et al., 2010). In 1968, the prevalence of epilepsy in Africa was about 4.8 to 40 ‰. In 1996, Diop and collaborators reported in Senegal a prevalence of epilepsy of 21 ‰ (Diop et al., 1996). In 2006, Ngoungou and collaborators estimated the prevalence in sub-Saharan Africa to be two or three time highest than the rate in developed world (Ngounou et al., 2007). In Cameroon, some epidemiological studies on epilepsy have shown that, the prevalence of epilepsy is estimated to vary from 5-136/1000. The highest ones are reported in some villages of the Cameroon Central Province located in the Sanaga and Mbam River Valley (Nchoji Nkwi & Tioko Ndonko, 1989; Dongmo et al., 2000; Preux et al., 2000; Boussinesq et al., 2002; Kamgno et al., 2003; Dongmo et al., 2004; Prischich et al., 2008). Cameroon is one of the countries most affected by epilepsy in Africa and in the world. Thus, epilepsy is among the major public health problems in Cameroon. In Africa and in Cameroon particularly, phytotherapy in traditional medicine still plays an important role in the management of diseases, mainly among populations with very low income (Geoffrey & Kirby, 1996). And phytotherapy relies on the use of a wide variety of plant species.
with these plants, very few were done to study their sedative and anticonvulsant properties. This study was undertaken to evaluate the anticonvulsant and sedative properties of these plants used in the treatment of insomnia and epilepsy in traditional medicine in Africa, particularly in Cameroon.
2. Materials and methods
2.1. Animals
Adult male mice (
Drugs were administered in a volume of 10 ml/kg of mice body weight. The study was conducted in accordance with the nationally (N°.FWA-IRB00001954) and internationally accepted principles for laboratory animal use and care. In diazepam or sodium thiopental- induced sleep tests, mice were divided into negative control group that received distilled water and four test groups that received different doses of the plant extracts. In anticonvulsant tests, there was one more group that received a known anticonvulsant compound and served as a positive control.
2.2. Plant material
A voucher specimen of each plant was authenticated by a botanist, Professor Mapongmetsem Pierre Marie, Department of Biological Sciences, University of Ngaoundéré and deposited at the National Herbarium of Cameroon in Yaoundé.
2.3. Preparation of the extracts
2.3.1. Decoction
10 g of each plant material were macerated for 1 h in an amount of distilled water (25, 50, 75, 100 or 150 ml) according to the plant. The mixture was boiled for 20 min. After cooling, the supernatant (decoction) was collected and filtered. The decoction of each plant was diluted in distilled water to obtain less concentrated solutions. In another experiment, the decoction was dried and the w/w yield of the extract was calculated (table 2). The decoctions were prepared according to the methods close to the ones used in traditional medicine.
2.3.2. Maceration
10 g of dried fruits of
2.4. Anticonvulsant tests
2.4.1. N-methyl-D-aspartate (NMDA) test
Six groups of 6 or 8 mice received different treatments. Group I (negative control) was treated with distilled water. Groups II to V (test groups) were treated with 4 doses of the plant extracts. Group VI (positive control) was treated with 3 mg/kg of CGP 37849 i.p. or 33 ηmol/kg of D-AP7 i.p. Mice were injected subcutaneously with NMDA, 75 mg/kg 1 h after administration of the different treatments. They were observed for 30 min. Animals that did not exhibit turning behaviour within the 30 min of observation were declared protected. Turning behaviour was characterised by two consecutive 360° cycles fulfilled by the same animal (Croucher et al., 1982; Ngo Bum et al., 2001; 2009a; 2009b; Schmutz et al., 1990).
2.4.2. Strychnine (STR) test
Six groups of 6 or 8 mice received different treatments as above, except that group VI (positive control) was treated with clonazepam (3 mg/kg, i.p.). Convulsions followed by death were induced in mice by the i.p. injection of 2.5 mg/kg STR nitrate 1 h after administration of the different treatments. The animals which survived more than 10 min after strychnine injection were qualified protected (Ngo Bum et al., 2001, 2009a).
2.4.3. Picrotoxine (PIC) test
Six groups of 6 or 8 mice received different treatments as above, except that group VI (positive control) was treated with clonazepam (0.4 mg/kg, i.p.). Clonic seizures were induced in mice by the i.p. injection of 7.5 mg/kg PIC 1 h after administration of the different treatments. The animals which did not convulse within the 15 min of observation after PIC injection were qualified protected (Lehmann et al., 1988; Ngo Bum et al., 2001).
2.4.4. Pentylenetetrazol (PTZ) test
Six groups of 6 or 8 mice received different treatments as above, except that group VI (positive control) was treated with clonazepam (0.1 mg/kg, i.p.). Clonic seizures were induced in mice by the i.p. injection of 70 mg/kg PTZ 1 h after administration of the different treatments. The animals that did not convulse within the 10 min from the injection of PTZ were qualified protected (Ngo Bum et al., 2001, 2009a, 2009b).
2.4.5. Isonicotinic hydrazide acid (INH) test
Six groups of 6 or 8 mice received different treatments as above, except that group VI (positive control) was treated with diazepam, 10 mg/kg (per os). Animals were injected i.p. with INH 250 mg/kg 1 h after the administration of the different treatments. The time to the onset of clonic or tonic seizures was recorded. (Bernasconi et al., 1988; Ngo Bum et al., 2001).
2.5. Diazepam or sodium thiopental-induced sleep in mice
Five groups of 6 or 8 mice received different treatments. Group I (negative control) was treated with distilled water and groups II to V (test groups) were treated with 4 doses of the plant extracts.The methods described by Beretz et al., (1978) and modified by Rakotonirina et al., (2001) were used. Sleep potentiating effects of the plant were studied in mice that received sodium thiopental or diazepam at a dose of 50 mg/kg (i.p.) 1 hour after the administration of the different treatments. The time between the loss of the straightening reflex and the regain of this reflex measured the sleeping time. The loss or the regain of the straightening reflex was measured by stimulating the external ear. When the mouse anterior paw does not move after stimulation with horsehair, the animal is sleeping. When the mouse is awakened, it moves and shakes its paw.
Leaves | Infusion Decoction | Insomnia, diabetes Spasms, Fever | Steroid, cardiac glycosides | Antimicrobial | Cameroon, Forest areas | |
Leaves Roots | Infusion | Convulsions, Epilepsy Sterility, diarrhoea, dysentery | anticonvulsant | Cameroon, Central Africa West Africa, South Africa | ||
Leaves | Decoction | Dizziness, migraines, headaches, rheumatism | Anti hypertensive | Cameroon, Central America | ||
Leaves | Applica-tion on head Decoction | Convulsions, rheumatism Arthritis | Flavonoids, antraquinones | Antinociceptive, anti-inflammatory antidiabetic | Central Africa | |
Leaves + Flowers Barks Roots | Decoction Infusion | Epilepsy, convulsions, Insomnia, agitation Headaches, Malaria fever Anxiety, schizophrenia | Sedative | Humid tropical areas | ||
Leaves Roots | Decoction | Convulsions, head aches Parasitic diseases | effect on purinergic neurotransmission | Cameroon, India | ||
Barks Roots | Epilepsy, Migraine, head aches Epilepsy, anxiety, schizophrenia | Angola, Cameroon Sudan, West Africa Central Africa | ||||
Fruits Leaves | Epilepsy Coughs, asthma, pains | Alkaloids, atropine | Africa, Asia, America, Europa | |||
Leaves Barks Roots | Decoction | Dizziness, schizophrenia, paralysis malaria, diarrhoea Epilepsy, Pains Paralysis | West Africa Central Africa | |||
Whole plant | Decoction | Convulsions, Insomnia Diarrhoea, amoeba, asthma, coughs, pains | Alkaloids, tannins | Anxiolytic | Africa continent | |
Sterm barks Fruts Leaves | Epilepsy, headache, fever, stomach-ache, diarrhoea Sleep disorders | beta-sistosterol butyrolactone, steroids, flacourtine, flavonoids, coumarine, terpenoids, polyphenols | Antiplasmodial Protection against liver toxicity | |||
Leaves Barks Roots | Infusion Powder | Headaches, fever, hypotension, diabetes, sickle cells Epilepsy, schizophrenia | Cameroon, Central Africa West Africa | |||
Leaves + Roots Roots | Convulsions, fever, hypertension Convulsions, | Cameroon, Central Africa, West Africa | ||||
Leaves, Barks Roots | Decoction | Headaches, schizophrenia, malaria Fever | Saponins, tannins, triterpenes | Antiinflamm-atory | Cameroon | |
Leaves | Infusion | Insomnia, muscle relaxant, | Antioxydant | Cameroon | ||
Leaves Barks | Decoction | Epilepsy, insomnia, anxiety states, headaches, migraine, agitation, fever Vermifuge, fever | Antitrypano-somal | Cameroon West Africa | ||
Leaves + flowers | Decoction | Epilepsy, convulsions, headaches, diarrhea, asthma | ricin | Neuroleptic like properties | Central Africa, West Africa | |
Barks Roots, Leaves | Epilepsy, schizophrenia Pains, Rheumatisms | Anxiolytic | Central Africa, West Africa | |||
Leaves Leaves and flowers Barks and Roots, | Fever, Conjunctivitis, Convulsions, gonorrhoea, bilharzias, stomach-aches, constipation, Epilepsy, syphilis, | 7-Methylphyscion Cassiamin A | Cameroon, Mali, Soudan, East and South Africa. | |||
Leaves Barks Roots | Decoction Decoction Macera-tion | Malaria, stomach-aches, leucorrhoea, Hepatitis, leucorrhoea Epilepsy, diarrhoea, leucorrhoea | Terminalin A Glaucinoic Acid | antimicrobial | ||
Roots | Epilepsy | Central Africa, | ||||
Barks Fruits Roots | Decoction | Epilepsy Convulsions Fevers, malaria | Saponins, tannins | Anticonvulsant | Angola, Cameroon, Sudan, West Africa, Central Africa | |
Roots Barks | Epilepsy, anti-parasitic diseases Head aches | Tannins, sterols | Savannah belt, open woodland in Africa | |||
Leaves Leaves + Barks | Decoction | Convulsions, Epilepsy, headaches, stress Head aches | Saponins, alkaloids, tannins, cadiac glycosides | Antimicrobial | Cameroon, Brazil |
2.6. Statistical analysis
Three parameters were measured: the protection against chemically-induced seizures, the latency to the onset of seizures (min) in INH test, the latency to the onset of sleep and the sleeping time (min) in the sleep potentiation test. Data of the control groups were compared to data of groups treated with the plants extracts and to data of the positive control groups. The statistical analysis were done using Fisher exact test and Anova followed by Dunnett (REGWQ). P<0.05 was considered significant.
2.7. Chemicals
D-2-amino-7-phosphonoheptanoate, Clonazepam, Isonicotinic hydrazide acid, N-methyl-D-aspartate, penthylenetetrazol, picrotoxine, sodium thiopental and strychnine are from Sigma Chemical, USA. Diazepam is from Roche, France.
3. Results
3.1. Sedative properties
The extracts of twenty one plants increased in a dose-dependent manner the sleeping time induced by sodium thiopental or diazepam. The most potent was
3.2. Anticonvulsant properties
3.2.1. On PTZ- induced convulsions
78.3% of plants extract were effective against PTZ-induced convulsions.
3.2.2. On STR- induced convulsions
The percentage of plants extracts that protected mice against STR-induced convulsions was
3.2.3. On PIC- induced convulsions
The percentage of plants extracts that protected mice against PIC-induced convulsions was
3.2.4. On NMDA- induced turning behaviour
The percentage of plants extracts that protected mice against NMDA-induced turning behaviour was 100%.
3.2.5. On MES- induced convulsions
The percentage of plants extracts that protected mice against MES-induced convulsions was 25%.
3.2.6. On INH- induced convulsions
The percentage of plants extracts that were effective against INH-induced convulsions in mice was 60%.
3.2.7. Plants efficacy
mice against the induced convulsions. 78% of plants protected both PTZ and STR-induced convulsions. 80.6% of plants protected both PTZ and PIC-induced convulsions. 80.8% of plants protected both STR and PIC-induced convulsions. Finally, 66.7% of plants at the same time protected PTZ, STR and PIC-induced convulsions.
3.2.8. Plants toxicity
4. Discussion and conclusions
The extracts of twenty one plants (91.3% of plants) increased the sleeping time induced by sodium thiopental or diazepam. The potentiation of the sleep time suggests the presence of sedative properties in the extracts of these plants (Rakotonirina et al., 2001; Ngo Bum et al., 2009a; 2009b). These sedative properties could be related to the presence of some components in the extracts activating the benzodiazepine, barbiturate and/or GABA receptors in the GABAA receptor complex (Rang et al., 1999; Bonin & Orser, 2008; Olkkola & Ahonen, 2008). Diazepam (benzodiazepine) and sodium thiopental (barbiturate) all bind to the GABAA receptor complex. Diazepam potentiates GABA-mediated inhibition via the increase in the affinity of this inhibitory neurotransmitter to its recognition sites within the GABAA receptor complex, by increasing the opening frequency of the chloride ion channel which leads to the enhancement of influx of chloride anions into the neuron and subsequent hyperpolarisation (Czapinsky et al., 2005). While sodium thiopental that act on the barbiturate binding site directly gate the chloride ion channel of the GABAA receptor complex. The sedative properties found here could explain the use of the twenty one plants in traditional medicine in Africa, particularly in Cameroon in the treatment of insomnia. The first eight more potent plants to induced sedation were:
The effect was moderate for the rest of plants. Tetrapleura tetraptera one of the plants studied showed also anticonvulsant properties in fruits (Nwaiwu, 1986; Ojewole, 2005). The antagonism of INH, PTZ- and PIC-induced seizures suggests the interaction of these plants with the GABA-ergic neurotransmission (De Deyn et al., 1992; Doctor et al., 1982; Löscher & Schmidt, 1988; Salih & Mustafa, 2008; Perez-Saad & Buznego, 2008). GABA is the main inhibitory neurotransmitter substance in the brain and is widely implicated in epilepsy. Inhibition of GABA-ergic neurotransmission or activity has been shown to promote and facilitate seizures, while enhancement of GABA-ergic neurotransmission is known to inhibit or attenuate seizures (Gale, 1992; Li-Ping et al., 2008). Moreover, some studies indicated that PTZ diminishes the GABAergic tone (Mcdonald & Baker. 1977; Ahmadiani, 2003), probably by a competitive antagonist action on the BZD receptors (Rehavi et al., 1982). Correspondingly, drugs that enhance GABAA-receptor neurotransmission, such as BZDs (White, 1997; Ahmadiani et al., 2003) can block seizures induced by PTZ. PIC is known to be a non competitive GABA antagonist exerting his effect by blocking the chloride channel in the GABAA receptor complex. Isoniazide can precipitate convulsions in patients with seizure disorders, and it is regarded as a GABA-synthesis inhibitor (Kale Shubhangi et al., 2010). The antagonism of STR -induced convulsions suggests the presence of anticonvulsant effect through glycine-STR-sensitive receptors (Findlay et al., 2002). Few plants extract antatagonized MES induced convulsions, by probably prolonging neurons sodium channels inactivation (Holmes, 2007). The results show no difference in plants inhibiting convulsions induced by PTZ, PIC and STR. GABA and glycine-STR-sensitive neurotransmission are equally involved. But very few plants produced their anticonvulsant activities by prolonging neurons sodium channels inactivation.
5. Conclusion
The purported anticonvulsant and sedative properties of the medicinal plants are scientifically shown. The ethnopharmacological study on Cameroon anticonvulsant and sedative medicinal plants is accurate in 90% of cases. A great amount of plants extract interacted through GABA and glycine-STR-sensitive neurotransmissions to inhibit convulsions. Many anticonvulsant plants also possess sedative properties. Twenty one plants possess sedative properties, but only eighteen plants could be used in traditional medicine in Africa in the treatment of insomnia. Eighteen plants possess at least moderate anticonvulsant effects, while five plants possess very good anticonvulsant properties. However only twenty medicinal plants could be used in the treatment of epilepsy. Three plants were found very toxic.
Acknowledgments
We would like to thank Professor AMVAM ZOLLO Paul Henri, Professor Ngounouno Ismaila, and Dr Megueni Clautilde for their support.
References
- 1.
Abbiw D. K. 1990 .185390437 United Kingdom. - 2.
Adeyemi O. O. Akindele A. J. Yemitan O. K. Aigbe F. R. Fagbo F. I. 2010 Anticonvulsant, anxiolytic and sedative activities of the aqueous root extract of Fresen. Journal of Ethnopharmacology,130 2 July, 2010),191 195 0378-8741 - 3.
Adjanohoun J. E. Ake Assi. L. Chibon P. De Vecchy H. Duboze E. Eyme J. Gassita J. N. Goudote E. Guinko S. Keita A. Koudogbo B. Le Bras M. Mourambou I. Mve-Mengome E. Nguema M. G. Ollome J. B. Posso P. Sita P. 1984 . Editions A.C.C.T.07540924 France. - 4.
Adjanohoun J. E. Aboubakar N. Dramane K. Ebot M. E. Ekpere J. A. Enow-Orok E. G. Focho D. Gbile Z. O. Kamanyi A. Kamsu-kom J. Keita A. Mbenkum T. Mbi C. N. Mbiele A. L. Mbome L. L. Mubiru N. K. Nancy W. L. Nkongmeneck B. Satabie B. Sofowora A. Tamze V. Wirmum C. K. 1996 Organization of African Unity Scientific, Technical and Research Commission; Centre National de Production de Manuels Scolaires,0716084 Novo, Benin. - 5.
Adzu B. Abbah J. Vongtau H. Karniyus 2003 Studies on the use of in malaria ethnopharmacy, Journal of Ethonopharmacology,88 2-3 261 267 0378-8741 - 6.
Agassounon Djipko. Tchibozo M. Sanon S. Damintoti S. K. Toukourou F. de Souza C. Gbeassor M. 2008 Appréciation des propriétés antiplasmodiale in vitro de Willd., une plante utilisée dans la médecine traditionnelle en Afrique. 15ème colloque sur la Pharmacopée et la Médecine Traditionnelles Africaines.15 156 160 Décembre 2008), Conseil Africain et Malgache pour l’Enseignement Supérieur (CAMES), Libreville, Gabon. - 7.
Ahmadiani A. Mandgary A. Sayyah M. 2003 Anticonvulsivant Effect of Flutamide on seizures induiced by pentylene tetrazole, involvement of benzodiazepine receptors. ,44 5 629 625 1528-1167 - 8.
Anete C. F. Miriam E. M. A. Da Costa. M. L. Ilza R. B. Bras H. D. O. Cunha C. D. 1998 Pharmacological Evaluation of Ricinine, a Central Nervous System Stimulant Isolated from Pharmacology, Biochemestry and Behavior,63 3 367 375 0091-3057 - 9.
Anuradha H. Srikumar B. N. Shankaranarayana Rao. B. S. Lakshmana M. 2008 reverses chronic stress-induced anxiety and mediates its action through the GABAA receptor benzodiazepine receptor-Cl2 channel complex. Journal of Neural transmission,11 3 35 42 1435-1463 - 10.
Arbonnier M. 2000 . Mali, Ouagadougou: Centre de Coopération Internationale en Recherche Agronomique pour le développement/Muséum national d’histoire naturelle/Union mondiale pour la nature (CIRAD/MNHN/UICN), IBSN0209 0914 Paris, France. - 11.
Beretz A. Haag-Berrurier M. Anton R. 1978 Choix de méthodes pharmacologiques pour l’étude des activités de l’aubépine. ,4 305 314 - 12.
Berhaut J. 1975 . Government of Senegal,183 184 Dakar, Senegal. - 13.
Bernasconi R. Klein M. Martin P. Christen P. Hafner T. Portet C. Schmutz M. 1988 Gamma-Vinyl GABA: comparison of neurochemical and anticonvulsant effects in mice.72 3 213 233 1435-1463 - 14.
Biholong M. 1986 . Thèse de doctorat. Université de Bordeaux III,10 50 France. - 15.
Bonin R. P. Orser B. A. 2008 GABAA receptor subtypes underlying general anesthesia.90 1 105 112 0091-3057 - 16.
Bouquet A. 1969 . ORSTOM, IRD, FDI 13972, Mémoire36 103 127 Montpellier, France. - 17.
Boussinesq M. Pion D. S. Kamgno J. 2002 Relationship between Onchocerciasis and epilepsy: a matched case control in the Mbam Valley, Republic of Cameroon. ,96 5 537 541 0035-9203 - 18.
Brenan J.P.M. 1959 . Agents de la Couronne, Londres, England. - 19.
Croucher J. M. Collins J. F. Meldrum B. S. 1982 Anticonvulsant action of excitatory amino acids antagonists.216 4548 899 902 1095-9203 - 20.
Czapinski P. Blaszczyk B. Czuczwar S. J. 2005 Mechanisms of Action of Antiepileptic Drugs.5 1 3 143 1568-0266 - 21.
Dalziel J. M. 1937 The Crown Agency for the Colonies, London, United Kingdom. - 22.
De Deyn P. P. D’Hooge R. Marescau B. Pei-Q Y. 1992 Chemical models of epilepsy with some reference to their applicability in the development of anticonvulsants. ,12 2 87 110 0920-1211 - 23.
Dimo T. Rakotonirina S. V. Tan P. V. Azay J. Dongo E. Cros G. 2002 Leaf methanol extract of prevents and attenuates the hypertension induced by high-fructose diet in wistar rats. Journal of Ethnopharmacology,83 4 183 191 0378-8741 - 24.
Diop A. G. Ndiaye M. Thiam A. et al. 1996 Filière des soins anti-épileptiques en Afrique. ,10 115 121 - 25.
Doctor S. V. Costa L. G. Muphur S. D. 1982 Effect of trimethyltin on chemically induced seizures, ,13 4 217 223 0378-4274 - 26.
Dongmo L. Ndo D. Atchou G. Njamnshi A. 2000 Epilepsie au Sud-Cameroun: enquête préliminaire dans le village Bilomo. ,93 3 263 275 0037-9085 - 27.
Dongmo L. Druet-Cabanac M. Moyou S. R. Zebaze D. R. Njamn-shi A. K. Sini V. Mapoure N. Echouffo T. J. Djeumen W. C. Ndumbe P. M. 2004 Cysicercosis and epilepsy: a casec ontrol study in MbamValley, Cameroon. ,97 2 Janvier 2003),105 108 0037-9085 - 28.
El -Mahmood A. M. Doughari J. H. Ladan N. 2008 Antimicrobial screening of stem bark extracts of against some enteric pathogenic microorganisms. African Journal of Pharmacy and Pharmacology,2 5 089 094 1996-0816 - 29.
Ezugwu C. O. Odoh U. E. 2003 Anticonvulsant activity of the root extract of . Journal of Tropical Medicinal Plants,4 1 51 55 1511-8525 - 30.
Findlay G. S. Wick M. J. Mascia M. P. Wallace D. Millier G. W. Harris R. A. Blednov Y. A. 2002 Transgenic expression of a mutant glycine receptor decreases alcohol sensitivity of mice. Journal Pharmacology Experimental Therapeutics,300 2 526 534 0022-3565 - 31.
Gale K. 1992 GABA and epilepsy: basic concepts from preclinical research. .33 5 S3 S12 0013-9580 - 32.
Geoffrey C. Kirby M. 1996 . Transaction of the Royal Society of Tropical Medicine and Hygiene,0035-9203 London, Great Britain. - 33.
Gusman-Gutierez S. L. Navarrete A. 2009 Pharmacological Exploration of the sedative mechanism of hesperidin identified as the Active principle of flowers. Planta medica,75 4 295 301 0032-0943 - 34.
Holmes G. L. 2007 Animal model studies application to human patients. ,69 24 S28 S32 0028-3878 - 35.
Hutchinson J. Dalziel J. M. 1958 . Crown Agents, Ed. 2 (Revised by R.W.J. Keay), The Whitefriars Press, London & Tonbridge, Great Britain. - 36.
Iwu M. M. 1993 . CRC Press, ISBN 084934266X, New York, USA. - 37.
Kale Shubhangi. S. Shete Rajkumar. V. Kore Kakasaheb. J. Patil Bhaskar. M. Bhutada Rupesh. N. Pattankude Vinod. 2010 Anticonvulsant activity of Glycyrrhizic acid in mice. ,2 2 0000-0974 - 38.
Kamgno J. Pion S. Boussinesq M. 2003 Demographic impact of epilepsy in Africa: results of a 10-years cohort study in a rural area of Cameroon.44 7 956 963 0013-9580 - 39.
Lehmann J. Hutchison A. Mc Pherson S. E. Mondadori C. Schmutz M. Sinton C. M. Tsai C. Murphy D. E. Steel D. J. Williams M. Cheney D. L. Wood P. L. 1988 CGS 19755, a selective and competitive N-methyl-D-aspartate-type excitatory amino acid receptor antagonist.246 1 65 75 1521-0103 - 40.
Li-Ping G. Xian-Yu S. Guan-Rong T. Kyu-Yun C. Zhe-Shan Q. 2008 The Synthesis and Anticonvulsant Activity of 1-Substituted-7-Methoxy-1,2,4-Triazolo [4, 3-a] Quinoline; ,32 2 181 189 1300-0837 - 41.
Lompo M. Nikiema J. B. Guissou I. P. Moës A. J. Fontaine J. 1998 The topical anti-inflammatory effects of chloroform extract from Khaya senegalensis stem barks.12 6 448 450 0095-1418 X. - 42.
Löscher W. Schmidt D. 1988 Which animal model should be used in the search for new antiepileptic drugs? A proposal based on the experimental and chemical consideration. ,2 3 145 181 0920-1211 - 43.
Macdonald R. L. Barker J. L. 1977 Pentylenetetrazole and penicillin are selective antagonists of GABA-mediated post-synaptic inhibition in cultured mammalian neurons. ,267 23 720 721 0028-0836 - 44.
Malgras D. 1992 . ACCT, Karthala,2-86537-377-0 France. - 45.
Mutasa S. L. Khan M. Jewers K. 1990 Methylphyscion and cassiamin A from the root bark of . Planta Medica.56 2 244 245 0032-0943 - 46.
Nazneen M. Abdul Mazid. Kundu J. K. Bachar S. C. Begum F. Datta B. K. 2009 Protective effects of parts extracts against paracetamol-induced hepatotoxicity in rats. Journal of Taibbah University for Science.2 1 1 6 1658-3655 - 47.
Nchoji Nkwi. P. Tioko Ndonko. F. 1989 The Epileptic among the Bamileke of Maham in the Nde Division, West Province of Cameroon. ,13 4 437 448 0016-5005 X. - 48.
Ngo Bum. E. Schmutz M. Meyer C. Rakotonirina A. Bopelet M. Portet C. Jeker A. Rakotonirina S. V. Olpe H. R. Herrling P. 2001 Anticonvulsant properties of the methanolic extract of (Cyperaceae). Journal of Ethnopharmacology76 2 145 150 0378-8741 - 49.
Ngo Bum. E. Taiwe G. S. Nkaissa L. A. Moto F. C. O. Seke E. P. F. Hiana I. R. Bailabar T. Rouyatou Seyni P. Rakotonirina A. Rakotonirina S. V. 2009a Validation of anticonvulsant and sedative activity of six medicinal plants. ,14 3 454 458 1525-5050 - 50.
Ngo Bum. E. Taiwe G. S. Moto F. C. O. Ngoupaye G. T. Nkantchoua G. C. N. Pelanken M. M. Rakotonirina S. V. Rakotonirina A. 2009b Anticonvulsant, anxiolytic and sedative properties of the roots of Smith in mice. Epilepsy and Behavior,15 4 434 440 1525-5050 - 51.
Ngounou E. B. Quet F. Dubreuil C. M. Marin B. Houinato D. Nubukpo P. Dalmay F. Millogo A. Nsengiyumva G. Kouna-Ndouongo P. Diagana M. Ratsimbazafy V. Druet-Cabanac M. Preux P. M. 2007 Épidémiologie de l’épilepsie en Afrique subsaharienne : une revue de la littérature. .16 4 Octobre-novembre-décembre 2006),225 238 Synthèse. - 52.
Njamnshi A. K. Bissek A. C. Yepnjio F. N. . Tabah E. N. Angwafor S. A. Kuate C. T. Déma F. Fonsah J. Y. Acho A. Kepeden M. N. Azinwi Y. H. Kuwoh P. B. Angwafor I. I. I. F. F. Muna W. F. 2010 A community survey of knowledge, perceptions, and practice with respect to epilepsy among traditional healers in the Batibo Health District, Cameroon. ,17 N°1, (10),95 102 PMID: 19932640. - 53.
Nwaiwu J. I. Akah P. A. 1986 Anticonvulsant activity of the volatile oil from the fruit of . Journal of Ethnopharmacology18 2 103 107 0378-8741 - 54.
Ogundiya M. O. Kolapo A. L. Okunade M. B. Adjumobi J. A. 2009 Assesment of phytochemical composition and antimicrobial activity of against some oral pathogens. Electronic journal of environmental, agricultural and food chemistry;8 7 466 471 1579-4377 - 55.
Ojewole J. A. 2005 Analgesic and anticonvulsant properties of (Taub) (Fabaceae) fruit aqueous extract in mice. Phytotherapy Research,19 12 1023 1029 1099-1573 - 56.
Okada R. Negishi H. 1989 The role of nitrotegmental gabaergic pathway in the propagation of pentylenetetrazol-induced seizures. .480 1 383 387 0006-8993 - 57.
Olkkola K. T. Ahonen J. 2008 Midazolam and other benzodiazepines. ,182 1 335 360 0378-8741 - 58.
Palgrave C. K. Drumond R. B. Eugene J. Palgrave C. M. 2003 . Struik Publishers,1-86872-389-5 Town South Africa. - 59.
Pathak P. Saraswathy Vora. A. Savai J. 2010 In vitro antimicrobial activity and phytochemical analysis of the leaves of . International Journal of Pharmaceutical Researches and Development,2 5 1 6 0974-9446 - 60.
Pérez-Saad H. Buznego M. T. 2008 Behavioral and antiepileptic effects of acute administration of the extract of the plant Lin (lady of the night). Epilepsy and Behaviour,12 3 366 372 1525-5050 - 61.
Pousset J. L. 1989 . Ellipses,2-72988-918-3 France. - 62.
Preux P. M. Tiemagni F. Fodzo L. Kandem P. Ngouafong P. Ndonko F. Macharia W. Dongmo L. Dumas M. 2000 Antiepileptic therapies in the Mi Province in Cameroon. ,41 4 432 439 1528-1167 - 63.
Prischich F. De Rinaldis M.. Flaminia B. Egeo G. Santori C. Zappaterreno A. Fattouch J. Di Bonaventura C. Bada J. Gianluca R. Pizzuti A. Cardona F. Sa’a V. V. Giallonardo A. T. D’Erasmo E. Pelliccia A. Vanacore N. 2008 High prevalence of epilepsy in a village in littoral province of Cameroon. ,82 2 200 210 0920-1211 - 64.
Rakotonirina S. V. Ngo Bum. E. Rakotonirina A. Bopelet M. 2001 Sedative properties of the extract of the rhizome of . Fitoterapia,72 1 22 29 0367-0326 - 65.
Rang H. P. Dale M. M. Ritter J. M. 1999 . Churchill Livingstone,0-44305-974-8 York, USA. - 66.
Raponda-Walker Sillans. R. 1961 Edition Sepia,2-90788-869-2 Gabon. - 67.
Rehavi M. Skolnick P. Paul S. M. 1982 Effects of tetrazole derivatives on [3H]-diazepam binding: in vitro: correlation with convulsant potency. ,78 3 353 356 0014-2999 - 68.
Salih M. A. Mustafa M. M. 2008 A substance in broad beans () is protective against experimentally induced convulsions in mice. Epilepsy and Behaviour,12 1 25 29 1525-5050 - 69.
Satyanaraya V. Kurupadanam G. L. Srimanaraya G. 1996 Photochemistry of plants. .30 4 1026 1029 0036-7326 X. - 70.
Saulnier P. 1998 , Edition SEPIA,978-2-90788-892-9 Saint-Maur, France. - 71.
Schmutz M. Portet C. Jeker A. Klebs K. Vassout A. Allgeier H. Heckendorn R. Fagg G. E. Olpe H. R. Van Riezen H. 1990 The competitive NMDA receptor antagonists CGP 37849 and CGP 39551 are potent, orally-active anticonvulsants in rodents.342 7 61 66 1432-1912 - 72.
Seema Z. 2006 Thèse doctorat Ph.D., Université de Karachi, Pakistan. - 73.
Sunday E. Atawodi Ogunbusola F. 2009 Evaluation of Anti trypanosomal Properties of Four Extracts of Leaves, Stem and Root Barks of Prosopis africana in Laboratory Animals.21 2 101 108 0795-8080 - 74.
White H. S. 1997 New mechanisms of antiepileptic drugs, In: ., (Ed.),1 30 Butterworth Heinemann,1-93386-416-8 USA. - 75.
Worapan S. Sornkanok V. Chuda C. Damri P. Siriprapa A. 2008 Pharmacognostic Investigation of the Leaves of and its DNA Fingerprints. Thai Pharmaceutical and Health Science Journal,4 1 9 14 0125-4685