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

ABSTRACT

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.

Email of correspondence: malamisani@gmail.com;

KEYWORDS:       Seizure, Dichloro phenyl propanamides, Nickel chloride.