Anticonvulsant and psychomotor activity of nitrendipine alone and in combination with phenytoin and valproate in rats.
The effect of nitrendipine (NTP) alone and in combination with phenytoin (PHT) and valproate (VPA) against maximal electroshock seizures (MES) was studied in rats. In addition, the psychomotor effects of NTP alone and in combination with PHT and VPA were evaluated using the following tests: a) rotarod performance; b) spontaneous motor activity; c) despair behavior; d) righting reflex; e) hole board test; and f) passive avoidance test. ED50 values of PHT, VPA and NTP were 13,255 and 3.6 mg/kg, respectively. When NTP was combined with PHT or VPA, the ED50 values decreased to 0.9 and 226 mg/kg, respectively. In the psychomotor function tests, for the same degree of protection (50%) afforded against MES, PHT or VPA produced a greater impairment in all the parameters compared to NTP alone or a combination of NTP with PHT or VPA. Furthermore, NTP reversed the depression and long-term memory loss induced by PHT and VPA. Thus, NTP was effective against MES in rats, potentiating the anti-electroshock activity of PHT and VPA and producing less impairment of psychomotor activity. Thus, the agent can be considered a potential antiepileptic warranting further studies.
Balakrishnan
S
S
Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Bhargava
V K
VK
Pandhi
P
P
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D004338:Drug Combinations; D004597:Electroshock; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009568:Nitrendipine / Q000008:administration & dosage / Q000494:pharmacology*; D010672:Phenytoin / Q000008:administration & dosage / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects; D012640:Seizures / Q000188:drug therapy / Q000209:etiology; D014635:Valproic Acid / Q000008:administration & dosage / Q000494:pharmacology*
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D004338:Drug Combinations; D014635:Valproic Acid; D010672:Phenytoin; D009568:Nitrendipine