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Desensitization and down‐regulation of brain alpha 2‐adrenoceptors by centrally acting antihypertensive drugs.
Author(s) -
Hamilton CA,
Yakubu MA,
Howie CA,
Jardine E.,
Reid JL
Publication year - 1990
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1990.tb05484.x
Subject(s) - guanabenz , clonidine , yohimbine , rilmenidine , endocrinology , medicine , alpha (finance) , imidazoline receptor , pharmacology , idazoxan , chemistry , agonist , prazosin , receptor , antagonist , construct validity , nursing , patient satisfaction
Rabbits were treated with intravenous clonidine (8 mumol kg‐1 day‐1), guanabenz (20 mumol kg‐1 day‐1), rilmenidine (80 mumol kg‐1 day‐1) or vehicle via osmotic minipumps. After 6 days treatment mean arterial pressure (MAP), pressor responses to intravenous alpha‐methyl noradrenaline and depressor responses to intracisternal clonidine were studied, and [3H]‐yohimbine binding to forebrain and hindbrain examined in vitro. Clonidine, guanabenz and rilmenidine had similar effects on MAP and caused a similar attenuation of the depressor response to intracisternal clonidine, but only guanabenz attenuated pressor responses to intravenous alpha‐methyl noradrenaline. Rilmenidine had no effect on [3H]‐yohimbine binding to brain membranes. Clonidine treatment decreased binding in hindbrain while guanabenz treatment decreased binding in both fore‐ and hindbrain. Thus, the depressor effects of chronic treatment did not correlate with the effects on [3H]‐ yohimbine binding sites in rabbit brain suggesting that the blood pressure lowering effects of many centrally acting antihypertensive drugs are not necessarily dependent on binding to the alpha 2‐ adrenoceptor site labelled by [3H]‐yohimbine.