Effect of clobenpropit on regional cerebral blood flow in rat hippocampus
Abstract
Aim: 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.
Conclusion: 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.
Keywords:
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.
Conclusion: 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.