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Biomedical subjects

M J RAND

Publications and source records attributed to M J RAND.

At least 19 recordsLinked to original sources
PubMed1964

SOME OBSERVATIONS ON THE PHARMACOLOGY OF ALPHA-METHYLDOPA.

alpha-Methyldopa in high concentrations impaired the responses of rabbit isolated ileum and guinea-pig isolated vas deferens to stimulation of the sympathetic nerves and to noradrenaline, but these preparations taken from animals previously treated with alpha-methyldopa showed no sign of impairment. Contractions of the cat nictitating membrane were reduced but not abolished by alpha-methyldopa. In cats, dogs and rats, pressor responses to noradrenaline were usually slightly increased by alpha-methyldopa. Pressor responses to tyramine were not affected consistently. alpha-Methyldopa, alpha-methyldopamine and alpha-methylnoradrenaline behaved like dopa, dopamine and noradrenaline respectively in restoring the responses of tissues from reserpine-treated animals to stimulation of the sympathetic nerves to the rabbit ileum, the guinea-pig vas deferens and the cat nictitating membrane and in restoring responses to tyramine of the cat blood pressure and nictitating membrane, and the rat blood pressure. The potency of alpha-methylnoradrenaline relative to noradrenaline ranged from one-half to one-ninth on various preparations. The results are discussed in relation to the antihypertensive action of alpha-methyldopa.

Animals↗
PubMed1963

Evidence for a competitive antagonism of guanethidine by dexamphetamine.

After guanethidine had blocked the response of the cat nictitating membrane to sympathetic nerve stimulation, dexamphetamine restored the responses to all frequencies of stimulation. Dexamphetamine antagonized the sympathetic nerve block by guanethidine in the isolated sympathetically innervated rabbit ileum; the evidence suggests that the antagonism was competitive. Dexamphetamine antagonized the sympathetic nerve block by guanethidine in the isolated hypogastric nerve-vas deferens preparation of the guinea-pig. Doses of dexamphetamine, larger than those required to antagonize the blocking action of guanethidine, abolished the responses of the nictitating membrane, ileum and vas deferens to nerve stimulation. Dexamphetamine did not influence the depletion of noradrenaline by guanethidine in the heart and spleen of rabbits. The hypothesis is advanced that both dexamphetamine and guanethidine act on the store of noradrenaline at sympathetic nerve endings.

Animals↗
PubMed1963

The adrenergic mechanism in the nictitating membrane.

The contractions of the nictitating membrane in response to postganglionic nerve stimulation have been studied in experiments in which cats' heads were perfused. When eserine was added to the perfusion fluid there was a rapid increase in the size of the contractions. In the presence of eserine the contractions produced by injecting acetylcholine into the perfusion fluid were greatly increased. When atropine was injected into the perfusion fluid the contractions caused by postganglionic nerve stimulation returned to the size before eserine was added. In experiments with cats anaesthetized with chloralose, atropine or hyoscine was given first and the effect of eserine on the response to submaximal postganglionic nerve stimulation was determined. Eserine slowly increased the responses to stimulation without increasing the contraction produced by injecting noradrenaline. In other experiments in which maximal stimuli were used, the relation of stimulus frequency to height of contraction was determined. The optimal frequency was low, being 5 to 10 shocks/sec. In the presence of hyoscine, eserine or neostigmine increased the response to stimulation; this increase was greater at lower frequencies, and lessened as the frequency rose to the optimal value.

Acetylcholine↗
PubMed1963

TACHYPHYLAXIS TO SOME SYMPATHOMIMETIC AMINES IN RELATION TO MONOAMINE OXIDASE.

Tachyphylaxis to the effects of indirectly acting sympathomimetic amines has been studied on the blood pressure of the cat, rabbit and rat, on the cat spleen and nictitating membrane and on the rabbit heart. The pressor responses to tyramine and to phenethylamine declined slowly with repeated injection; the extent of tachyphylaxis induced by these amines depended on the dosage and on the frequency of injection. The pressor responses to alpha-methyltyramine and to dexamphetamine (alpha-methylphenethylamine) declined rapidly with successive injections. The tachyphylaxis induced by one indirectly acting sympathomimetic amine is crossed to others, but not to directly acting amines, such as noradrenaline. In animals treated with nialamide, a drug which inhibits monoamine oxidase, the tachyphylaxis induced by tyramine and by phenethylamine was similar to that produced by their alpha-methyl derivatives in normal animals. Similar results were obtained when the responses to indirectly acting sympathomimetic amines were studied on the cat spleen in situ and on the rabbit heart in vitro. Indirectly acting sympathomimetic amines impaired the responses of the cat nictitating membrane to sympathetic nerve stimulation; this effect was most evident with alpha-methylated amines.

Animals↗
PubMed1962

Triethylcholine compared with other substances affecting neuromuscular transmission.

Triethylcholine (triethyl-2-hydroxyethyl ammonium) has been compared, in its actions on neuromuscular transmission, with the motor end-plate blocking drugs tubocurarine and decamethonium, with the anticholinesterase neostigmine, and with the closely related drug tetraethylammonium. The experiments were carried out on conscious rabbits and mice, on the tibialis anterior muscle of cats under chloralose anaesthesia and on the isolated phrenic nerve-diaphragm preparation of the rat. Anticholinesterase activity was determined manometrically using the Warburg apparatus. Triethylcholine possessed a slight curare-like action, but this effect was shown to be too weak and transient to contribute to the slowly developing and long-lasting transmission failure which occurs selectively in frequently excited nervemuscle preparations and in exercised conscious animals. It was confirmed that the site of the blocking action of triethylcholine was pre-junctional. Triethylcholine often produced a slight potentiation of the contractions before blocking them. This effect was not due to a depolarizing or an anticholinesterase action, and it was concluded that the slight initial facilitating action of triethylcholine on neuromuscular transmission was due to an increase in the quantity of acetylcholine released by the nerve impulse. Tetraethylammonium was much more powerful than triethylcholine in this respect. The pre-junctional transmission failure produced by triethylcholine could not be explained simply on the basis that an initial excessive release led to exhaustion of transmitter.

Acetylcholine↗
PubMed1962

Sympathetic vasodilatation in the rabbit ear.

Changes in the blood content of a 1 cm(2) portion of the intact rabbit's ear were studied with transillumination and a photocell. Stimulation of the post-ganglionic sympathetic nerves produced a decrease in blood content, attributable to vasoconstriction, followed by an increased blood content, attributable to vasodilatation. The vasodilatation was enhanced by eserine and decreased by atropine. Guanethidine abolished the vasoconstriction but not the vasodilatation. After the ganglion had been decentralized by degeneration of the pre-ganglionic sympathetic nerves the vessels had an increased sensitivity to acetylcholine and the vasodilatation in response to sympathetic stimulation was enhanced. It is concluded that sympathetic stimulation results in the liberation of acetylcholine which causes vasodilatation.

Acetylcholine↗