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Characterization of central H 2 receptors mediating cardiovascular activity by means of three histamine H 2 receptor antagonists: MK‐208, BMY‐25368, and cimetidine in the rat
Author(s) -
Poulakos Jennifer J.,
Gerges Elizabeth N.,
Gertner Sheldon B.
Publication year - 1991
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430220408
Subject(s) - histaminergic , cimetidine , histamine , histamine h2 receptor , pharmacology , agonist , receptor , histamine receptor , medicine , endocrinology , chemistry , antagonist
Stimulation of central histamine H 1 and or H 2 receptors with histaminergic drugs results in a dose‐related pressor response and bradycardia in conscious, freely‐moving rats. Two recently developed peripheral histamine H 2 antagonists, MK‐208 and BMY‐26368, as well as cimetidine, were evaluated with respect to their ability to block the cardiovascular actions of central histamine H 2 receptors. These drugs do not readily cross the blood brain barrier, therefore, they were administered intracerebroventricularly (i.c.v.). The ability of these agents to attenuate the cardiovascular effects of the H 2 agonist impromidine was studied in conscious, freely‐moving rats. Blood pressure and heart rate were monitored directly via indwelling carotid catheters, and drugs were administered i.c.v. through permanently implanted cannulae. All of the H 2 antagonists tested induced a transient hypertensive response that lasted approximately 15 min. MK‐208 (30 μg) partially blocked the central cardiovascular actions of impromidine. Unlike other histaminergic agents, MK‐208 produced a tachycardia and a profound hyperactivity which slowly developed into seizures. BMY‐25368 and cimetidine failed to antagonize the cardiovascular actions of impromidine. These results demonstrate that cimetidine and BMY‐25368, established peripheral H 2 antagonists, did not block central H 2 receptors, suggesting that central and peripheral H 2 receptors may be pharmacologically distinct.