EFFECTS OF BRETYLIUM, RELATED QUATERNARY AMMONIUM COMPOUNDS, AND MITOSIS INHIBITORS ON THE DEGENERATION ACTIVITY IN THE SYMPATHETICALLY INNERVATED PERIORBITAL SMOOTH MUSCLE IN THE CONSCIOUS RAT

Abstract

The results presented here emanate from pharmacological studies on the degeneration contraction of the sympathetically innervated periorbital smooth muscle in the rat. This transient degeneration activity is due to the release of stored transmitter from the degenerating nerve endings. Drugs from two pharmacologically different groups of substances were found to cause a real delay of the degeneration transmitter release. One of the groups consisted of the adrenergic neuron blocker bretylium and some other quaternary ammonium compounds. The delaying effect of these drugs was most prominent after injections given close to the expected onset of the degeneration transmitter release. The delaying action seems to be exerted in the distal parts of the neurons since the drugs are effective when given locally in the effector organ. The delaying effect is reduced by tricyclic antidepressants and indirect sympathomimetic amines. The other group of delaying drugs were the mitosis inhibitors colchicine, vinblastine, and vincristine which are known to inhibit the microtubular intra-axonal flow. These drugs delay the degeneration activity if given early after denervation. The delaying effect of colchicine decreases gradually with an increasing time interval between the denervation and the injection. The delaying effect of colchicine is absent after injections given 6 h or more after the denervation. Hypothetically, the mitosis inhibitors cause a delay by slowing down an “axotomy message” conveyed by the intra-axonal flow. The rate of transport of the signal seems to be about 4 mm/h. It is proposed that there are two latencies of the processes starting the degeneration transmitter release in the periorbital smooth muscle of the rat. One latency (about 5 h) is due to the transport of the axotomy message and is colchicine-sensitive. The other latency (about 8 h) which is due to the progress of local processes in the nerve endings is presumably bretylium-sensitive.