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PubMed1957

The relation between sedation and body temperature in the mouse.

Chlorpromazine and reserpine reduce locomotor activity and prolong pentobarbitone hypnosis in mice. Both these effects are shown to be proportional to the fall in body temperature produced by these drugs. Other agents are shown to reduce body temperature and potentiate pentobarbitone. At ambient temperatures of 32 degrees C. neither chlorpromazine nor reserpine is hypothermic or sedative. It is concluded that sedative effects in the mouse at ordinary room temperatures are related to the hypothermic properties of these drugs. At 36 degrees C., while reserpine fails to potentiate pentobarbitone, chlorpromazine still does so.

Anesthesia↗
PubMed1957

Metabolic and other effects of reserpine upon smooth and skeletal muscle.

Reserpine increased the concentration of potassium ions in the fluid bathing the isolated frog sartorius muscle. The effect of reserpine upon respiration and upon glycolysis in rabbit intestinal muscle has been investigated using the Warburg "Direct" method. After a latent period, reserpine (50 mug./ml.) depressed respiration but did not affect glycolysis in gut muscle. These results, together with previous observations, may point to an effect of reserpine upon carbohydrate metabolism.

Animals↗
PubMed1957

The concentration of adrenaline in the plasma of rabbits treated with reserpine.

Doses of 1 to 2.3 mg./kg. of reserpine given intravenously to rabbits raised the plasma adrenaline. The noradrenaline concentrations were too near the threshold of the method to decide whether any alterations followed the injection of reserpine. Control experiments, in which blood samples were taken from rabbits but no drug was given, showed only a very slight rise in adrenaline concentration after the first bleeding.

Animals↗
PubMed1957

Effects of reserpine on blood-pressure responses evoked from the hypothalamus.

Different areas of the hypothalamus were stimulated by a stereotaxic technique before and after reserpine in unanaesthetized cats. Reserpine in a dose of 1 mg./kg. body weight increased the threshold of stimulation of hypothalamic areas in cats giving an initial pressor response. It decreased the threshold of stimulation of areas of the hypothalamus in animals giving an initial depressor response. Reserpine thus appeared to affect the hypothalamus directly in two ways. It depressed the sympathetic centres in the diencephalon and facilitated the parasympathetic ones.

Animals↗
PubMed1958

The action of sympathomimetic amines on heart rate in relation to the effect of reserpine.

When the heart-lung preparation is made from a dog treated with reserpine, catechol amines such as noradrenaline and isoprenaline have a greater effect on the rate of the heart than they have in a preparation from a normal dog. Other sympathomimetic amines such as tyramine and ephedrine, on the other hand, are found to have lost their action. Since treatment with reserpine has been shown to cause the store of noradrenaline in the heart to disappear, and the infusion of noradrenaline into the preparation made from a reserpine-treated animal restores the action of tyramine, it is concluded that substances like tyramine and ephedrine normally act by liberating noradrenaline from the store, and do not act directly. Cocaine, like reserpine, increases the effect of noradrenaline and decreases the effect of tyramine on the heart rate; it appears to block the release of noradrenaline from the store in the heart.

Amines↗
PubMed1958

The depressor action of dopamine and adrenaline.

Dopamine is a pressor agent in the spinal cat, but causes a fall of blood pressure in the guinea-pig and rabbit under urethane anaesthesia. When guinea-pigs and rabbits are injected with reserpine, which depletes the vessel walls of noradrenaline, dopamine then becomes pressor. If an intravenous infusion of noradrenaline is given the depressor action returns. An intravenous infusion of vasopressin does not have this effect.A strip of rabbit aorta is caused to contract by noradrenaline and by dopamine, but if dopamine is added at the height of a noradrenaline contraction it causes relaxation.Adrenaline causes a fall of blood pressure in the cat under ether with vagi cut. However, in a reserpine-treated cat its action is pressor. The depressor action is restored during an infusion of noradrenaline. Noradrenaline has thus been shown to cause a vasomotor reversal of dopamine and of adrenaline.

Animals↗
PubMed1959

Some effects of reserpine and hydraliazine upon tissue respiration and the concentration of adenosine nucleotides in certain tissues.

The effects of reserpine and hydrallazine upon the oxygen uptake of preparations of rat brain, liver, and kidney and rabbit aorta have been investigated using the Warburg "Direct" method. In these tissues reserpine did not significantly stimulate respiration at any of the doses used. Concentrations of 10 or 50 mug./ml. had no significant effect upon respiration, but higher doses (330 mug./ml.) depressed it in all the tissues studied. This effect was also seen in rat brain at a reserpine concentration of 100 mug./ml. which had no significant effect in other tissues. Hydrallazine (50 or 100 mug./ml.) depressed respiration in all tissues studied. Stimulation at lower doses was not seen.After sublethal doses of reserpine, depletion of energy rich phosphate compounds occurred in brain and liver but not in skeletal muscle and heart. Hydrallazine also depleted brain of energy rich phosphate compounds, but did not affect liver, heart, or skeletal muscle. The bearing of these results on the mode of action of reserpine and hydrallazine is discussed.

Adenosine↗
PubMed1959

The effect of reserpine on the acetylcholine content of different areas of the central nervous system of the dog.

The acetylcholine content of the frontal and temporal lobes, hippocampus, hypothalamus, cerebellum and spinal cord was estimated in 18 dogs 3 hr. after the intravenous administration of reserpine. Another group of 7 dogs served as control. After reserpine (0.5 mg./kg. body weight) there was an increase of acetylcholine in all the areas under study except in the hippocampus. The increase was specially marked in the hypothalamus. In the hippocampus, however, reserpine caused a significant decrease of acetylcholine.

Acetylcholine↗
PubMed1959

The effects of reserpine and other agents upon leptazol convulsions in mice.

Reserpine and tetrabenazine reduced the survival time of mice infused with leptazol. This effect was antagonized by pretreatment with iproniazid. The survival time of iproniazid-treated mice was prolonged by 5-hydroxytryptophan but not by 3:4-dihydroxyphenylalanine. These findings suggest a relation between leptazol sensitivity and brain levels of 5-hydroxytryptamine.

5-Hydroxytryptophan↗
PubMed1959

Mechanism of action of reserpine in producing gastric haemorrhage and erosion in the mouse.

Gastric haemorrhage was produced regularly in mice within 6 hours of the subcutaneous injection of a large dose (2 to 10 mg./kg.) of reserpine or of deserpidine. Rescinnamine, syrosingopine (SU-3118), and tetrabenazine (Ro 1-9569) were less active. Gastric haemorrhage was also produced within 6 hours when 5-hydroxytryptamine (10 mg./kg.) was injected every half-hour. Neither reserpine nor 5-hydroxytryptamine produced gastric haemorrhage in mice which had been vagotomized by tying the oesophagus at the cardio-oesophageal junction or which had been pre-treated with iproniazid. Amphetamine was less effective than iproniazid in preventing gastric haemorrhage after reserpine, and the following drugs were ineffective: cocaine, methyl phenidate (Ritalin), amarin, caffeine, nikethamide, lysergic acid diethylamide and its 2-bromo derivative (BOL148). Gastric haemorrhage was not observed in mice which had been given substantial doses of atropine or of hexamethonium before reserpine. The incidence of haemorrhage was substantially reduced by treatment with an antacid mixture. It is concluded that reserpine-like drugs cause gastric haemorrhage by a mechanism which has an important central component and which involves the liberation of 5-hydroxytryptamine.

Amphetamine↗