ANTICONVULSANT PROPERTIES OF ISOMERS OF DICHLOROPHENYL AMINO PROPANAMIDES IN MICE
|SANI MALAMI1*, ABDULLAHI YUNUSA IDRIS2, ABDULLAHI HAMZA YARO1, ASMA’U NASIR HAMZA2 JOSEPH AKPOJU ANUKA3, ISA MARTE HUSSAINI4
1.Department of Pharmacology and Therapeutics, Bayero University, Kano, Nigeria.
2.Department of Pharmaceutical and Medicinal Chemistry, Ahmadu Bello University, Zaria, Nigeria.
3.Department of Pharmacology and Therapeutics, Ahmadu Bello University, Zaria, Nigeria.
4. Department of Pharmacology and Toxicology, University of Maiduguri, Nigeria
Afr. J Pharm Res Dev; Volume 12(2): 226-232 ; 2020
Antiepileptic drug development is a dynamic process, affording many research opportunities. Continued efforts are being made in the development of antiepileptic drugs employing a range of strategies, including modification of the structures of existing drugs, targeting novel molecular substrates and non-mechanism-based drug screening. This research was aimed at evaluating the anti-seizure effects of three isomers of diclorophenyl propanamides (DCP), viz; 2,3- (DCP23)-, 2,5- (DCP25) and 3,4- (DCP34) dichloro-substituted phenyl propanamides, using chemically- and electrically- induced seizure models. In 4-aminopyridine-induced seizure test, there was no protection offered by the three compounds, but DCP34 at doses of 50 mg/kg and 25 mg/kg exhibited significant (p < 0.05) increase in the onset of seizures. The compounds did not offer protection in strychnine-induced seizure test. In picrotoxin-induced seizure test, DCP23 and DCP25 offered protection against clonic convulsion of 66.7% and 83.3% at 50 mg/kg; 50.0% and 66.7% at 25 mg/kg, respectively. Single oral administration (100 mg/kg) of the compounds (DCP23, DCP25 and DCP34) produced 37.5%, 50% and 0.0% protections respectively against tonic hind limb extension (THLE) while a 5-day administration offered higher protection of 50%, 75% and 25% respectively. When DCP23 or DCP25 (25 mg/kg), was co-administered with nickel chloride (5 mg/kg), the percentage protection against PTZ-induced seizure was better (66.67% and 33.33% respectively) than when administered separately. These compounds possess anticonvulsant activity and could be optimized to develop potential lead compound with antiepileptic effect.
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KEYWORDS: Seizure, Dichloro phenyl propanamides, Nickel chloride.