Effects of drugs on tremor and increase in brain acetylcholine produced by oxotremorine in the rat

Abstract

In rats the effect of drugs on oxotremorine tremor and oxotremorine‐induced increase in brain acetylcholine has been investigated. Reserpine, (±)‐α‐methylmetatyrosine and diethyldithio‐carbamic acid, drugs which have in common the ability to decrease tissue noradrenaline concentration, inhibited oxotremorine tremor without preventing the oxotremorine‐induced increase in brain acetylcholine. (±)‐p‐chlorophenylalanine, a depletor of tissue 5‐hydroxytryptamine, did not inhibit oxotremorine tremor. Phenoxybenzamine and propranolol inhibited oxotremorine tremor, and propranolol was without effect on oxotremorine‐induced increase in brain acetylcholine. The toxicity of oxotremorine was increased by reserpine and phenoxybenzamine. The significance of these findings is discussed with regard to the mode of action of oxotremorine.

Effects of Some Cholinergic, Adrenergic and Serotoninergic Compounds, Glutamic Acid and GABA on Hippocampal Seizures

“…The excitatory action of Ach agrees with data on its microelectrophoretic application on the hippocampal units (Biscoe and Straughan, 1966 ;Curtis and Crawford, 1969), as well as with observations on seizure threshold in diverse species (Cox and Potkonjak, 1970;Mahon and Brink, 1970). The effects of eserine and atropine on their own suggest that endogenous hippocampal Ach may play a physiologic role.…”

“…There are, besides, numerous reports on the role of these substances in seizures in diverse regions of the brain, even though these reports are sometimes contra dictory (Boggan and Seiden, 1971;Cox and Potkonjak, 1970;De la Torre et al, 1970;Knaape and Wiechert, 1970;Laguzzi et al, 1970;Pasquini et al, 1968;Schlesinger et al, 1968\S z e e ta l, \9 1 \ ,Wood et al, 1969.…”

Antioxotremorine Action of Propranolol

“…Cox & Potkonjak (1970) postulated that oxotremorine-tremor was mediated through peripheral propranolol-sensitive receptors perhaps of the same kind as those which on stimulation enhance physiological tremor (Marsden et al, 1967). The present results indicate that such peripheral propranolol-sensitive receptors may be located at the skeletal myoneural junction.…”

“…Propranolol diminishes tremor in patients with Parkinson's disease (Owen & Marsden, 1965;Marsden, Meadows, Lange & Watson, 1967) and inhibits oxotremorine-induced tremor in mice and rats (Jacobi, 1957;Agarwal & Bose, 1967;Cox & Potkonjak, 1970). Some other central effects of oxotremorine, including its analgesic and hypothermic effects are not affected by propranolol (Hermansen, 1968) and it has therefore been suggested that the antitremor action of propranolol is mediated peripherally (Marsden et al, 1967).…”

The Pharmacology of Sedative/Hypnotics, Alcohol, and Anesthetics: Sites and Mechanisms of Action

“…Possibly related are propranolol's alleviation of withdrawal tremors (ZILM et aI., 1975), its antianxiety effects (KELLNER et aI., 1974), and its augmentation of ethanol effects (ALKANA et aI., 1976). Propranolol also reportedly blocks the tremors induced by oxotremorine (BRIMBLECOMBE and PINDER, 1972;AGARWAL and BOSE, 1967;JACOBI, 1967;SINHA, 1967, 1968;Cox and POTKONJAK, 1970;WATANABE et aI., 1971).…”