Effect of clobenpropit on regional cerebral blood flow in rat hippocampus.
OBJECTIVE
The effect of clobenpropit on regional cerebral blood flow (rCBF) was investigated in the rat hippocampus.


METHODS
rCBF was determined in the hippocampus by the hydrogen clearance method. The blood pressure was measured by a tail-cuff plethysmograph.


RESULTS
Intracerebroventricular (icv) injection of clobenpropit (20, 50 microg), a representative H3-antagonist, dose-dependently and significantly increased rCBF in the hippocampus. The increase of rCBF induced by clobenpropit was enhanced by metoprine (1, 2 mg/kg), a selective histamine N-methyltransferase inhibitor; however, was antagonized by an H3-agonist, (R)-alpha-methylhistamine (5 microg), an H(1)-antagonist, mepyramine (5-10 mg/kg), and an H2-antagonist, zolantidine (10 mg/kg). Clobenpropit caused no apparent effects on blood pressure even at a high dose of 50 microg.


CONCLUSIONS
These results suggest that brain endogenous histamine may contribute to increase rCBF in the rat hippocampus via both the post-synaptic H1-, H2-receptors and the pre-synaptic H3-receptor.
Chen
Z
Z
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310031, China. chenzfl@hotmail.com
D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000098:blood supply*; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D011739:Pyrimethamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology*
D017442:Histamine Agonists; D006633:Histamine Antagonists; D007093:Imidazoles; D008761:Methylhistamines; C006308:metoprine; C069357:alpha-methylhistamine; D013890:Thiourea; C086108:clobenpropit; D011739:Pyrimethamine