title: Alpha-blocking potencies of antihypertensive agents (prazosin, terazosin, bunazosin, SGB-1534 and ketanserin) having with quinazoline or quinazolinedione as assessed by radioligand binding assay methods in rat brain.
abstract: The comparative effects of antihypertensive agents, quinazoline or quinazolinedione residues (prazosin, bunazosin, terazosin, SGB-1534, and ketanserin), on the binding of [3H]prazosin, [3H]p-aminoclonidine and [3H]dihydroalprenolol([3H]DHA) to alpha 1-, alpha 2-, and beta-adrenoceptors in the rat brain were examined using radioligand binding assay methods. pA2 values were also obtained in the isolated rat aorta (alpha 1-adrenoceptor) using phenylephrine as an agonist. A strong inhibition by these drugs of [3H]prazosin binding to alpha 1-adrenoceptors was observed, while the inhibition of [3H]DHA binding to beta-adrenoceptors and [3H]p-aminoclonidine binding to alpha 2-adrenoceptor was found to be very weak. The rank order of antagonistic potencies of these drugs against the alpha 1-adrenergic receptors was determined by inhibition constants (Ki) with SGB-1534 = prazosin = bunazosin greater than terazosin greater than ketanserin. The pA2 value of these drugs, in contrast, had prazosin with higher pA2 value than that of SGB-1534. From these two different types of experiments, it was clear that these drugs antagonized alpha 1-adrenoceptors even in the central nervous system, and the side chains bound to quinazoline and quinazolinedione residues may play an important role in the antagonistic potencies for alpha 1-adrenoceptors in the central nervous system as in the peripheral tissues.
authors.affiliation: Department of Pharmacology, Niigata College of Pharmacy, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tsuchihashi
authors.forename: T
authors.initials: T
authors.lastname: Nagatomo
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003000:Clonidine / Q000031:analogs & derivatives / Q000378:metabolism; D004082:Dihydroalprenolol / Q000378:metabolism; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D011224:Prazosin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D011799:Quinazolines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; C016986:apraclonidine; C042712:SGB 1534; C041226:Terazosin; D007650:Ketanserin; C018176:bunazosin; D003000:Clonidine; D011224:Prazosin