Interaction of cyclazocine and the sympathetic nervous system

Cyclazocine, a benzomorphan derivative narcotic agonist-antagonist, reduced the uptake of tritiated norepinephrine and reduced the recovery of [3H]3,4-dihydroxymandelic acid, but did not significantly alter the recovery of [3H]normetanephrine in the rat heart in vivo. Cyclazocine also reduced endogenous levels of norepinephrine in the rat heart. Comparatively, desipramine reduced the uptake of [3H]norepinephrine, the recovery of [3H]3,4-dihydroxymandelic acid, and the recovery of [3H]normetanephrine in the rat heart in vivo. Further, cyclazocine added to the perfusion medium or administered systemically reduced the uptake of radiolabeled norepinephrine by the isolated rat heart. The cyclazocine-induced decrease in the accumulation of [3H]norepinephrine in the rat heart in vivo and in vitro presumably is due to an alteration of sympathetic function through the inhibition of neuronal uptake. It is further suggested that cyclazocine has other actions on the sympathetic nervous system, such as promoting neurotransmitter release.