Reversal of mu-opioid-mediated respiratory depression by alpha 2-adrenoceptor antagonism.

The present study was performed in order to evaluate the effects of the selective alpha 2-adrenoceptor antagonist 6-chloro-2,3,4,5-tetrahydro-3-methyl-1H-3-benzazepine (SK&F 86466) on dermorphin-induced analgesia, respiratory depression and inhibition of locomotor activity in the conscious rat. Intracerebroventricular (icv) administration of dermorphin (3 nmol/rat) decreased respiration rate and relative ventilatory minute volume maximally by 38% and 50% of baseline respectively. SK&F 86466 dose-dependently reversed the dermorphin-induced depression of ventilatory parameters, while SK&F 86466 exerted no effect on dermorphin-induced analgesia or depression of locomotor activity due to catalepsia. It appears, therefore, that alpha 2-adrenoceptors selectively interact with mu 2-opioid-receptor mediated effects, such as respiratory depression, but are not involved in the modulation of mu 1-opioid-related effects, such as supraspinal analgesia and depression of locomotor activity.