The relationship between tremor and change in brain acetylcholine concentration produced by injection of tremorine or oxotremorine in the rat

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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.

Section: Brain Acetylcholine Estimationmentioning

confidence: 99%

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

Cox

Potkonjak

1970

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“…It could exert its effects by causing a release of acetylcholine from endogenous stores. Cox & Potkonjak (1969) found that oxotremorine does, in fact, cause an increase in brain acetylcholine in rats but there is a 15 min time lag between dosing and the observed rise in acetylcholine. As the hypertensive response to oxotremorine is almost immediate, it does not therefore seem likely that this effect is due to the latter mechanism of action, although it is possible that acetylcholine could be redistributed, thus increasing its availability at muscarinic receptors, with no immediate change in total brain content.…”

Section: Effect Of Vagotomymentioning

confidence: 99%

Oxotremorine‐induced hypertension in the anaesthetized rat

Walker

Weetman

1970

Summary1. Oxotremorine exerts an action on peripheral cholinoceptors in the anaesthetized rat. After the blockade of peripheral cholinoceptors with the quaternary atropine derivative, atropine methylbromide, oxotremorine produced a rise in arterial blood pressure and tachycardia. 2. The rise in arterial pressure and tachycardia was absent in rats that had been pithed or had undergone high spinal cord transection. 3. A non-quaternary atropine derivative antagonized these cardiovascular effects. 4. Drugs which inhibit activity of the sympathetic nervous system antagonized the oxotremorine-induced hypertension and tachycardia. 5. It is concluded that the rise in arterial pressure and tachycardia seen in the anaesthetized rat treated with a quaternary derivative of atropine is due to an action of oxotremorine on the central nervous system at a supraspinal level, resulting in an increase in activity of the efferent sympathetic nervous system.

“…This drug has marked parasympathomimetic actions, blockade of which can be used to measure the peripheral anticholinergic potency of atropine-like drugs. In addition it produces muscular tremors in a variety of species of animals, and although there has been much discussion as to its mode of action in producing these tremors there is now evidence (Bebbington & Brimblecombe, 1965;Cox & Potkonjak, 1969a, b) to suggest that it is due to an interaction with central acetylcholine receptors analogous to peripheral muscarinic receptors. Thus, blockade of oxotremorine-induced tremors can be used to give a measure of central anticholinergic potency.…”

Section: Introductionmentioning

confidence: 99%

The protective actions of some anticholinergic drugs in sarin poisoning

Brimblecombe

Green

Stratton

et al. 1970

Summary The central and peripheral anticholinergic activities of a series of drugs comprising atropine, hyoscine, caramiphen and one of its analogues, and three glycollic acid esters, have been measured. The ability of the same drugs used alone, and in conjunction with N‐methyl pyridinium‐2‐aldoxime methanesulphonate (P2S), to protect mice, rats and guinea‐pigs from the lethal effects of sarin has been assessed. No correlation was found to exist between central or peripheral anticholinergic activity and ability to protect from sarin. On the indirectly stimulated isolated rat phrenic nerve‐diaphragm preparation all drugs with the exception of hyoscine caused potentiation of responses to low frequency stimulation but partial block of responses to high frequency stimulation. The drugs did not reverse the effects of sarin on the phrenic nerve‐diaphragm preparation. It is concluded that a pharmacological action other than an anticholinergic one is involved, in part, in the protective actions against sarin of some of the drugs studied. Whether their effects on skeletal muscle are of any relevance in this respect is unresolved.