Neurotoxic convulsions induced by histamine H2 receptor antagonists in mice

摘要: Convulsive potency was evaluated to investigate the mechanism of neurotoxic convulsion induced by histamine H2 receptor antagonists (H2 blockers). Four blockers, cimetidine (721-1236 nmol), ranitidine (477-954 famotidine (7.4-44 and nizatidine (226-603 nmol) were administered intracerebrally (i.c.) mice. Dose dependency clonic and/or tonic observed, ED50 values convulsive occurrence for cimetidine, ranitidine, famotidine, 997, 662, 23.4, 404 nmol, respectively. Intraperitoneal pretreatment muscimol, aminooxy acetic acid, diazepam, (+/-)2-amino-7-phosphonoheptanoic acid (APH), or (+)MK801 suppressed after i.c. administration but had no effect on convulsion. Furthermore, threshold concentration in brain determined constant rate infusion not affected APH, MK801. Ed50 four blockers correlated well with EC50 gastric secretion inhibition. The concentrations 11 2.5 microM, respectively, which similar dissociation constants from inhibition output From these results, can be GABAergic glutamatergic anticonvulsants, while may associated blockade directly GABA glutamate-mediated neurotransmission.