Interaction between R 56865 and alpha-adrenoceptors in the pithed rat.
In pithed normotensive rats, the benzothiazolamine derivative R 56865 in high doses exhibits a competitive antagonism of alpha 1-adrenoceptor-mediated vasoconstrictions. The absence of a depression of the maximum of the dose-response curve of ST 587 and the very moderate attenuation of the maximal B-HT 920-induced increase in diastolic blood pressure (BP) confirms the lack of major calcium entry blocking properties of R 56865 for alpha-adrenoceptor-activated calcium channels in vitro. In doses up to 10(-5) mol/kg, the interaction of R 56865 with the sympathetic neurotransmission can solely be explained by alpha 1-adrenoceptor blockade. This was confirmed by the comparable antagonism of the selective alpha 1-adrenoceptor antagonist prazosin in a concentration of 6 x 10(-8) mol/kg. In contrast to the isolated rat aorta, where R 56865 showed an allosteric interaction with the NA binding site on the alpha 1-adrenoceptor, R 56865 acts like an alpha 1-adrenoceptor antagonist of the competitive type in vivo.
Koch
P
P
Janssen Research Foundation, Neuss, F.R.G.
Schneider
J
J
Fruh
C
C
Wilhelm
D
D
Wilffert
B
B
Peters
T
T
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001381:Azepines / Q000494:pharmacology; D052160:Benzothiazoles; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013844:Thiazoles / Q000494:pharmacology*; D014439:Tyramine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000889:Anti-Arrhythmia Agents; D001381:Azepines; D052160:Benzothiazoles; D010880:Piperidines; D011942:Receptors, Adrenergic, alpha; D013844:Thiazoles; C030655:St 587; C024763:talipexole; C054551:R 56865; D008729:Methoxamine; D003000:Clonidine; D009638:Norepinephrine; D014439:Tyramine; D011224:Prazosin