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Effect of repeated administration of centhaquin, a centrally acting hypotensive drug, on adrenergic, cholinergic (muscarinic), dopaminergic, and serotonergic receptors in brain regions of rat
Author(s) -
Gulati Anil,
Hussain Ghazala,
Srimal Rikhab Chand
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.430230404
Subject(s) - endocrinology , medicine , serotonergic , muscarinic acetylcholine receptor , dihydroalprenolol , chemistry , hypothalamus , blood pressure , cholinergic , striatum , adrenergic , receptor , antagonist , serotonin , dopamine , partial agonist
Centhaquin, a hypotensive drug, produced a dose dependent decrease in blood pressure and heart rate in urethane anesthetized rats. The hypotensive and bradycardic effects of centhaquin were absent in cervial sectioned rats. There was no effect on blood pressure or heart rate upon intrathecal injection of centhaquin in normal rats. These results indicate that centhaquin is a centrally acting hypotensive drug with supraspinal site of action. Centhaquin (0.1 mg/kg) or its vehicle was administered orally to rats for 2 months. The blood pressure was recorded indirectly in unanesthetized rats by the plethysmographic tail cuff method. The animals were sacrificed, decapitated, and specific areas of the brain, like corpus striatum, cerebral cortex, hypothalamus, and medulla were dissected out and membranes prepared for binding studies. The mean blood pressure of rats before starting the treatment was comparable in control and treated groups. A significant decrease in mean blood pressure was observed in centhaquin treated rats. Chronic administration of centhaquin in rats produced alterations in central α‐adrenergic, dopaminergic, and serotonergic (5‐hydroxytryptamine 1 [5‐HT 1 ]) receptors. In the cerebral cortex corpus striatum of centhaquin treated rats, B max and K d values of 3 H‐dihydroergocryptine binding did not change, while in hypothalamus and medulla, centhaquin treatment increased the B max value by 52% and 86%, respectively. There was no change in the K d values. Centhaquin treatment did not affect B max and K d values of 3 H‐dihydroalprenolol binding to β‐adrenergic receptors, 3 H‐quinuclydinyl benzylate binding to cholinergic (muscarinic), and 3 H‐spiperone binding to 5‐hydroxytryptamine 2 (5‐HT s ) receptors in any of the four brain regions. In the cortex, centhaquin treatment decreased the B max value (25%) but did not change the K d values was produced in corpus striatum, hypothalamus, and medulla of 3 H‐spiroperidol binding to dopaminergic receptors. Cerebral cortex, corpus striatum, and hypothalamus of centhaquin treated rats did not show any change in B max or K d values of 3 H‐5‐HT binding to 5‐HT 1 receptors. In medulla, centhaquin treatment increased the B max value (41%) of HT 1 receptors but had no effect on K d values. It can be concluded from the present study that centhaquin, a centrally acting hypotensive drug, acts on several neurotransmitter receptors. The brain regions mainly involved in cardiovascular regulation, hypothalamus and medulla, show up‐regulation of αadrenergic and serotonergic (5‐HT 1 ) receptors and may play a role in the mechanism of hypotensive action of centhaquin.