Recovery of alpha-adrenoreceptor mediated responses and binding site number after intravenous benextramine in the rabbit.
The densities of [3H]-prazosin and [3H]-clonidine binding sites were determined in spleen and brain membrane preparations from rabbits treated 1 to 48 h previously with benextramine (5 mg/kg). In other rabbits pressor responses to phenylephrine and BHT 920 were examined 1 to 72 h after benextramine administration. After benextramine there was a reduction in the density of both [3H] prazosin and [3H] clonidine binding sites in spleen and a non-parallel shift in pressor dose response curves to selective alpha 1- and alpha 2-adrenoreceptor agonists. Recovery of in vivo responses and binding site densities were relatively slow. No reduction in the maximum density of either [3H] prazosin or [3H] clonidine binding sites in brain was found after intravenous administration of benextramine. It is concluded that after intravenous administration benextramine binds irreversibly to peripheral alpha 1- and alpha 2-adrenoreceptors in the rabbit but fails to cross the blood brain barrier in appreciable quantities and bind to central alpha-adrenoreceptors. Recovery of in vivo responses was more rapid than that previously observed after alpha-adrenoreceptor blockade with phenoxybenzamine. The longer time course of recovery after phenoxybenzamine may be a result of redistribution of this lipophilic drug from fat.
Furnace
G
G
Hamilton
C A
CA
Reid
J L
JL
Sumner
D J
DJ
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D003000:Clonidine / Q000378:metabolism; D003538:Cystamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D008566:Membranes / Q000378:metabolism; D010643:Phenoxybenzamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013997:Time Factors
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001381:Azepines; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D010656:Phenylephrine; C029998:benextramine; C024763:talipexole; D003000:Clonidine; D003538:Cystamine; D011224:Prazosin