Cardiovascular and behavioral actions of centrally administered cimetidine

The cardiovascular and behavioral actions of cimetidine, injected into the lateral ventricle, were studied in conscious, freely moving rats. Cimetidine produced a dose-dependent pressor response accompanied by decreases in heart rate and increases in pulse pressure. At doses of 25-100 micrograms, cimetidine produced sedation; however, when 200 micrograms was injected, tremor was observed in all animals. If cimetidine was administered twice within 30 min to the same animal, tachyphylaxis in response to any of these actions was never evident. Although histamine produced similar pressor actions when administered intraventricularly, these effects were always subject to tachyphylaxis. The actions of cimetidine were not altered by central pretreatment with the H1 antagonist chlorpheniramine. A possible hypothesis of the central mechanism by which cimetidine produces these effects is discussed.