Antioxotremorine Action of Propranolol

Abstract

I The influence of propranolol on the neuromuscular, tremor-producing and muscarinic effects of oxotremorine was examined. 2 In the isolated rat phrenic nerve-diaphragm preparation the neuromuscular blocking effect of oxotremorine was inhibited by propranolol in a dose-dependent manner. 3 Propranolol intensified the paralytic effect of tubocurarine in the rat diaphragm and prevented antagonism of tubocurarine paralysis by tetraethylammonium. 4 Propranolol was devoid of any curare-like effect in the isolated rectus abdominis muscle of the frog. SVasodepressor responses to oxotremorine in rats and spasmogenic responses to oxotremorine in guinea-pig ileum were not antagonized by propranolol. 6 A dose-dependent antagonism of oxotremorine-induced tremor in mice was observed after pretreatment with propranolol and it is suggested that this effect is due to an antagonism of a presynaptic effect of oxotremorine at skeletal neuromuscular junctions.

Enhancement by Oxotremorine of Acetylcholine Release From the Rat Phrenic Nerve

“…It is worth mentioning that not only propranolol (Ganguly, 1976) and the cholinolytic anti-Parkinson drugs (Das & Ganguly, 1977) antagonize the skeletal myoneural (extrafusal) effect of Oxo-T, but also TK 174, a quarternary compound, inhibits tremor even though it does not permeate the central nervous system (Leszkovszky & Tardos, 1971). In view of these reports it is tempting to conclude that the effects at the motor nerve junction, the muscle spindle, and the cholinergic synapse from motor axon collaterals to Renshaw cells could contribute to the tremorogenic action of Oxo-T.…”

“…The tremorogenic agent, oxotremorine (Oxo-T), blocks neuromuscular transmission at the rat phrenic nerve junction (Ganguly & Chaudhuri, 1970); this effect is inhibited by propranolol (Ganguly, 1976). A prejunctional action of Oxo-T seemed likely.…”

ANTI‐TREMOR ACTION OF C10DICHOL, A PERIPHERAL ACETYLCHOLINE SYNTHESIS INHIBITOR

“…The simple subjective scoring method of Spencer (1965) was used, as results obtained with it closely paralleled those obtained with an objective tremor recording device (Ganguly, 1976 (Figure 2).…”

“…This effect of Oxo-T is mediated at least in part through a presynaptic cholinergic CH3 dominance at the myoneural junction resulting from activation of presynaptic muscarinic receptors on the motor nerve endings (Das et al, 1978;Ganguly & Das, 1979). With the use of Oxo-T as a screening model, neuromuscular involvement has been demonstrated in the antitremor action of propranolol (Ganguly, 1976) and of TK-174 (1,1-bis-(4-amino-phenyl} propyl-(3}amine), a substance that does not permeate the blood brain barrier (Leszkovszky & Tardos, 1971).…”

“…There is increasing evidence in the literature for skeletal neuromuscular involvement in the genesis as well as the prevention of Parkinson-like features induced by chemical agents that are recommended for screening procedures in the evaluation of antiParkinson drugs (Cahen & Lynes, 1951;Everett, Blockus & Shepperd, 1956;Ganguly, 1976;Das & Ganguly, 1977;Das, Ganguly & Vedasiromoni, 1978;Ganguly, Nath, Ross & Vedasiromoni, 1978; Ganguly & Das, 1979). Of these agents, the muscarinic agonist oxotremorine (Oxo-T), is unique in producing the typical features of Parkinson's disease (Friedman & Everett, 1964;Jenden, 1968).…”