Effect of dihydropyridines and diphenylalkylamines on pentylenetetrazol-induced seizures and cerebral blood flow in cats

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Abstract
✓ Nimodipine, a dihydropyridine that interacts with a Ca++ channel-associated binding site, when delivered (30 to 150 µg/kg) intra-arterially (ia) to enflurane-anesthetized cats, produced a dose-dependent suppression of seizures evoked by pentylenetetrazol. A comparable suppression was produced by clonazepam (1 to 30 µg/kg, ia). Phenytoin was maximally effective only at nearly lethal doses (90 mg/kg, ia). Verapamil, a diphenyl-alkylamine that interacts with a separate Ca++ channel-associated site, at the maximum nonlethal dose (6 mg/kg, ia) resulted in a mild facilitation of seizure activity. The drug vehicle used in these studies (50% polyethylene glycol-400) had no effect when given alone. Regional cerebral blood flow (rCBF) as measured by the clearance of xenon-133 was markedly elevated immediately after the onset of seizure activity (89 ± 3 to 168 ± 4 ml/100 gm/min). Concurrent with their resolution of the seizure activity, both nimodipine and clonazepam reduced rCBF to near preseizure levels and pres...