Centrally mediated pressor response to metiamide as a result of GABA-receptor antagonism.
The mechanism of the pressor response to metiamide was examined in anesthetized cats. Intravenous administration of metiamide had no effect on blood pressure. Infusion into the lateral ventricle (10 mg/kg/min for 10 min), caused a marked pressor response which was due to an increase in sympathetic outflow since pretreatment of cats with guanethidine completely prevented it. In a rat brain synaptosome preparation, both metiamide and cimetidine displaced [3H] CABA. These data strongly suggest that metiamide increases blood pressure in the cat through a central mechanism involving GABA-receptor antagonism.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002415:Cats; D002927:Cimetidine / Q000378:metabolism; D008785:Metiamide / Q000378:metabolism / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D011963:Receptors, GABA-A; D013890:Thiourea / Q000031:analogs & derivatives*
D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D008785:Metiamide; D002927:Cimetidine; D013890:Thiourea