Presynaptic dual inhibitory actions of guanabenz on adrenergic transmission

Abstract

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.