INTERACTION OF CATECHOLAMINES WITH LEVORPHANOL AND MORPHINE IN THE MOUSE EYE

¹ Department of Psychiatry, New York University Medical Center, New York
² Department of Psychiatry, New York University Medical Center, New York, New York

Reserpine has been found to block the formation of the transient lenticular opacities normally produced in mice by a large dose of levorphanol. Small doses of catecholamines, metaraminol or phenylephrine, but not amphetamine, serotonin, methacholine or histamine, restore the lenticular activity of this analgesic. These data suggest interaction of levorphanol and adrenergic substances to produce lenticular opacities. The interaction within the mouse eye was quantitatively studied by dropping concentrated solutions of epinephrine on the eye followed by intraperitoneal injection of levorphanol. The incidence of opacity rose in the treated eye with the higher concentrations of epinephrine. By varying the doses of the two drugs, a reciprocal relation between topical epinephrine and injected levorphanol was demonstrated. Mice quickly became tolerant to the lenticular effect of levorphanol, but simultaneous administration of norepinephrine failed to restore the full effect of the narcotic. Because uptake of labeled levorphanol into the lenses and brains of tolerant mice was found similar to that in the controls, it is suggested that tolerance to the lenticular action of levorphanol may actually represent insensitivity or tolerance to norepinephrine.