Presynaptic dual inhibitory actions of guanabenz on adrenergic transmission.
Actions of guanabenz, clonidine and guanethidine on adrenergic transmission were studied in rabbit atria and ilea with intact nerves. While guanabenz 3 X 10(-6) M and clonidine 3 X 10(-7) M inhibited to a similar degree atrial positive chronotropic responses to nerve stimulation at 2 Hz, no inhibition was seen at 10 Hz. Phentolamine 3 X 10(-6) M completely antagonized the inhibition by clonidine, but a partial antagonism was seen against guanabenz. Cocaine 10(-5) M prevented the phentolamine-resistant inhibition by guanabenz. Guanethidine 10(-5) M inhibited the responses to 2 and 10 Hz. In ilea, guanabenz 10(-5) M inhibited frequency-independent relaxation responses to 2-20 Hz. Clonidine 10(-5) M inhibited preferentially the responses to lower frequencies. After the temperature of the bathing solution was kept at 4 degree C during the period of drug application, guanabenz no longer produced an inhibition of the transmission, whereas clonidine produced the usual inhibition. Thus, guanabenz appears to have both presynaptic alpha-receptor stimulating and adrenergic neuron blocking actions.
D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006143:Guanabenz / Q000494:pharmacology*; D006145:Guanethidine / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009411:Nerve Endings / Q000187:drug effects; D011817:Rabbits; D013268:Stimulation, Chemical; D013564:Sympathetic Nervous System / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D006146:Guanidines; D006143:Guanabenz; D003000:Clonidine; D006145:Guanethidine