Tremorine: Its Effect on Amines of the Central Nervous System

Friedman, Alexander H.; Aylesworth, Robert J.; Friedman, Gertrud

doi:10.1126/science.141.3586.1188

Cited by 30 publications

(7 citation statements)

References 6 publications

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“…Vas (1966), however, did not observe any effect of propranolol in Parkinsonian tremor.Friedman (1963) andFriedman, Aylesworth &Friedman (1963) have shown that tremorine lowers the noradrenaline levels in the brains of rats, mice and guinea-pigs but fails to do so in rabbits, which do not show tremor after the administration of tremorine.These findings indicate that brain catecholamines may have a role in causing tremor and the present work was undertaken to study their role in, and the effect of, a recent adrenergic f,-receptor blocking drug-namely, dextro-N-isopropyl-para-nitrophenylethanolamine (d-INPEA)-on tremorine and harmaline induced tremor in mice. …”

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confidence: 99%

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A Study of the Role of Brain Catecholamines in Drug Induced Tremor

Agarwal

Böse

1967

British Journal of Pharmacology and Chemotherapy

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In a recent study, Owen & Marsden (1965) have shown that adrenaline increases and that the adrenergic ft-receptor blocking drugs, pronethalol and propranolol, diminish tremor in patients with Parkinson's disease. Vas (1966), however, did not observe any effect of propranolol in Parkinsonian tremor.Friedman (1963) andFriedman, Aylesworth &Friedman (1963) have shown that tremorine lowers the noradrenaline levels in the brains of rats, mice and guinea-pigs but fails to do so in rabbits, which do not show tremor after the administration of tremorine.These findings indicate that brain catecholamines may have a role in causing tremor and the present work was undertaken to study their role in, and the effect of, a recent adrenergic f,-receptor blocking drug-namely, dextro-N-isopropyl-para-nitrophenylethanolamine (d-INPEA)-on tremorine and harmaline induced tremor in mice. METHODSTremor was recorded by a modification of the method of Ahmed & Taylor (1959). A perforated plastic box 5 in x 3 in x 2 in was bolted to a 31 in brass rod (* in diameter), which in turn was fixed into the position of the stylus of a high impedance (6,000Q) electromagnetic gramophone pick-up. Lateral movements of the box were converted by the pick-up into electrical changes, which were amplified and recorded on one channel of a Grass four channel electroencephalograph. The amplification level was kept at a minimum. The paper speed was 15 mm/sec. The whole device was kept in a sound-proof booth. Sixty male mice, weighing between 22-27 g, fed in the morning on the day of experiment, were used. They were placed in the box, one at a time, for 10-15 min before each experiment, in order to acclimatize them. This ensured a very low baseline due to reduced spontaneous activity of the mice. After a control period, one of the two tremorogenic drugs was injected intraperitoneally (tremorine 20 mg/kg and harmaline 30 mg/kg) and movements were recorded every 5 min for 60 min. After establishing that in the doses given, all the mice showed tremor after the drugs, they were divided into six groups of 10 mice.The mice in each group received one of the drugs used in the present study, intraperitoneally, and each group then was further divided into two subgroups of five animals each, for challenging with tremorine and harmaline. The effects of these tremorogenic drugs were then followed for a period of 1 hr.The various drugs used for modifying tremor were: reserpine (Serpasil; Ciba), alpha-methylmeta-tyrosine (Merck, Sharp and Dohme), pargyline (Abbot), propranolol (I.C.I.), d-INPEA and I-INPEA (Selvi).

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“…Friedman (1963) andFriedman, Aylesworth &Friedman (1963) have shown that tremorine lowers the noradrenaline levels in the brains of rats, mice and guinea-pigs but fails to do so in rabbits, which do not show tremor after the administration of tremorine.…”

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A Study of the Role of Brain Catecholamines in Drug Induced Tremor

Agarwal

Böse

1967

British Journal of Pharmacology and Chemotherapy

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“…At 160 C there was a clear increase, while at 6°C there was suggestive evidence of an increase. These findings may present an explanation for the conflicting reports quoted in the introduction (Friedman et al, 1963;Whittaker & Walaszek, 1964).…”

Section: Brain Aminesmentioning

confidence: 82%

The Effect of Ambient Temperature on the Actions of Tremorine on Body Temperature and on the Concentration of Noradrenaline, Dopamine, 5‐hydroxytryptamine and Acetylcholine in Rat Brain

Cox

Potkonjak

1967

British Journal of Pharmacology and Chemotherapy

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“…Everett et al (8) suggested that the probable site of produc tion of tremorine tremor is at subcortical level. Evidences so far available show that there is disturbed me tebolism of catecholamines in the brain of patients with Parkinson's disease (9) and in rats brain after ad ministration of tremorigenic dcse of tremorine (10). The abolition of tremor by propranolol seems to sup port that catecholamines has some role in the causation of tremorigenic tremor and that of Parkinson's disease.…”

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Anti-Tremor Action of Propranolol (Inderal)

Achari¹,

Sinha²

1967

Jpn.J.Pharmacol

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Herring (1) reported that pronethalol reduces the tremor in Parkinson's disease. Marsden and Owen (2,3) demonstrated that pronethalol and the newer beta blocking agent-propranolol both abolished the in crease in tremor of patients with Parkinson's disease during infusions of epinephrine. The present study was undertaken to explore the possibility of propranolol (Inderal) as a blocking agent in tremorine (1,4 dipyrrolidino-2-butyne) induced tremor in albino rats.Methods: Experiments have been carried out in albino rats (Central Drug Research Institute, Lucknow, Strain) of both sexes weighing between 100-150 g at room temperature (average of 30°C). The concentra tion of drug was such that required dose could be given in volume of 0.5 ml/ 100 g of body weight. Groups of ten animals were pretreated subcutaneously with test drug 30 minutes prior to Rota rod test (4). Fifteen mg/kg of tremorine was given intraperitoneally 20 minutes prior to the test. Anti-tremor effect of com pound was measured by determining of the ability to restore the capacity of tremorine injected rats to remain on slowly rotating rod (5 rotations per minute) during one minute period. The median effective dose (ED50) was calculated by the method of Miller and Tainter (5). The incidence of salivary secretion and diarrhoea was also noted.Results: Atropine sulphate is a powerful antagonist against tremorine and hence was chosen as standard drug (6). Various doses ranging from 2 to 8 mg/kg body weight were given to eight groups of rats. The ED,, obtained from such experiments was 1.30±0.291 mg/kg. The drug completely antagonized tremor, salivation and diarrhoea. The ED,, dose was taken as unity and the potency ratio of the compound has been calculated in respect of atropine.

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Tremorine: Its Effect on Amines of the Central Nervous System

Cited by 30 publications

References 6 publications

A Study of the Role of Brain Catecholamines in Drug Induced Tremor

A Study of the Role of Brain Catecholamines in Drug Induced Tremor

The Effect of Ambient Temperature on the Actions of Tremorine on Body Temperature and on the Concentration of Noradrenaline, Dopamine, 5‐hydroxytryptamine and Acetylcholine in Rat Brain

Anti-Tremor Action of Propranolol (Inderal)

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