Effect of 1,1-Dimethyl-4-Phenylpiperazinium Iodide on Peristaltic Reflexes of Isolated Guinea Pig Ileum

Chen, Graham; Portman, Ruth

doi:10.3181/00379727-85-20844

Cited by 6 publications

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“…This nicotine-like substance causes a stimulation of autonomic ganglia which is short-lived and not followed by paralysis (Chen & Portman, 1954); consequently, the same effect can be produced repeatedly, and the compound appeared ideally suited to test the hypothesis (Burn et al, 1959) that the action of nicotine on the vessels of the rabbit ear, the cat nictitating membrane and piloerectors, and other organs supplied with sympathetic fibres was produced indirectly by a release of noradrenaline and not due to a direct action of the drug on the ganglia. The site of the stores from which the noradrenaline would be released could be either the sympathetic neurones or the tissue itself.…”

Section: Dimethylphenylpiperazinium Iodidementioning

confidence: 99%

Effect of Drugs on the Noradrenaline Content of Brain and Peripheral Tissues and Its Significance

Sanan

Vogt

1962

British Journal of Pharmacology and Chemotherapy

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Large single doses of methoserpidine (12 mg/kg) given to rabbits lowered the noradrenaline content of sympathetic ganglia but not that of brain; no sedation was observed. Cats responded to doses ranging from 12 to 0.5 mg/kg with loss of noradrenaline from ganglia as well as from brain, and were sedated by the drug. The effect in man resembles that in the rabbit. Only within the group of reserpine-like drugs do sedation and loss in hypothalamic noradrenaline run parallel. These effects are therefore not causally related. Guanethidine lowers the noradrenaline content of sympathetic ganglia (cats and rabbits), but this effect does not explain the blocking action of the drug on the adrenergic nerve. Effects on the noradrenaline of the brain are variable and may be caused reflexly rather than by direct central action of guanethidine. Repeated intravenous injections of dimethylphenylpiperazinium iodide for a period of 4 hr did not produce any significant change in the noradrenaline content of ganglia or brain of rabbits. In contrast, dexamphetamine (20 mg/kg) produced a small but significant mean fall in noradrenaline content of the superior cervical ganglia and in that of the brain, but the effects were not seen in every rabbit. Prolonged administration of the mono-amine oxidase inhibitors pheniprazine and phenylhydrazinobutane raised the noradrenaline content of the brain of rabbits but not that of cats, whereas it raised the noradrenaline of the ganglia of cats but not (or rarely) that of rabbits. The question of correlation between a rise in the noradrenaline content of the brain and certain clinical signs is discussed. Finally, a comparison is made in rabbits between the changes produced by drugs in the noradrenaline content of the heart and of the superior cervical ganglion. The changes run parallel and are only occasionally more pronounced in the heart.A study was made of the changes-in the noradrenaline content of sympathetic ganglia and brain produced by a series of drugs. The first section deals with drugs which have pharmacological actions on different parts of the postsynaptic sympathetic neurones. Two of these drugs, methoserpidine (10-methoxydeserpidine) and guanethidine, cause hypotension, and the question arose whether this effect can be explained by changes in the noradrenaline content of the peripheral sympathetic neurones. A second point was to ascertain whether these drugs have any action on the brain. The actions of the two other drugs, the nicotine-like compound dimethylphenylpiperazinium iodide, which stimulates sympathetic ganglia, and

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Section: Dimethylphenylpiperazinium Iodidementioning

confidence: 99%

Effect of Drugs on the Noradrenaline Content of Brain and Peripheral Tissues and Its Significance

Sanan

Vogt

1962

British Journal of Pharmacology and Chemotherapy

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“…The evidence suggests that, in the small intestine of the rabbit or guinea-pig, DMPP blocks the inhibitory effects of periarterial nerve stimulation by an adrenergic neurone blocking action; this blocking action can occur with concentrations of DMPP which are, in most instances, lower than those used to stimulate ganglia (Chen et al, 1951;Leach, 1957;Ling, 1959;Brownlee & Johnson, 1963), to block ganglia (Chen & Portman, 1954;Leach, 1957;Ling, 1959;Brownlee & Johnson, 1963) or to block the skeletal neuromuscular junction (Kaller, 1956;Ling, 1959). SUMMARY 1.…”

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“…When the possible sites and mechanisms of the sympathetic blocking action of DMPP are considered, the known ganglion-blocking property of the drug (Chen & Portman, 1954;Leach, 1957;Ling, 1959;Brownlee & Johnson, 1963) must be taken into account. Are there ganglionic synapses in the periarterial sympathetic nerves, an anatomical arrangement known to occur in the sympathetic nerves to the vas deferens of the guinea-pig (Bentley & Sabine, 1963;Birmingham & Wilson, 1963), and could the sympathetic blocking action of DMPP be the result of ganglion blockade ? That the periarterial sympathetic nerves of the rabbit Finkleman preparation are postganglionic fibres was confirmed by experiments using concentrations of hexamethonium greater than those known to block ganglia (Feldberg, 1951); these concentrations of hexamethonium had no blocking action on the sympathetic inhibition.…”

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confidence: 99%

An Analysis of the Blocking Action of Dimethylphenylpiperazinium Iodide on the Inhibition of Isolated Small Intestine Produced by Stimulation of the Sympathetic Nerves

Birmingham

Wilson

1965

British Journal of Pharmacology and Chemotherapy

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“…It is therefore a " nicotinelike" drug, but unlike nicotine it appears to have little blocking action on ganglia, even in large doses. For this reason it has been used by Chen et al (1951) and by Fakstorp and Pederson (1954) in preference to nicotine as an agonist in estimating the efficiency of ganglion-blocking agents on plain muscle preparations, such as guinea-pig ileum. Most ganglionic stimulators, like nicotine and tetramethylammonium, block ganglionic transmission in large doses or after repeated administration of small doses, so that dimethylphenylpiperazinium seemed to be an exceptional drug and worthy of further investigation.…”

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confidence: 99%

“…In particular my object was to discover under what conditions, if any, dimethylphenylpiperazinium would block ganglion cells. Chen and Portman (1954) showed that dimethylphenylpiperazinium iodide caused a block of the peristaltic reflex of the guinea-pig ileum set up as described by Trendelenburg (1917). Leach (1957) confirmed this finding, and he also showed that, when a maintained contraction of the nictitating membrane of the cat was produced by stimulation of the preganglionic x cervical sympathetic, dimethylphenylpiperazinium injected intra-arterially caused a lessening of the contraction, which then slowly returned.…”

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confidence: 99%

Actions of Dimethylphenylpiperazinium

Ling

1959

British Journal of Pharmacology and Chemotherapy

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The actions of 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) have been studied to discover under what conditions a blocking action could be seen. Dimethylphenylpiperazinium has a stimulant action on autonomic ganglia, stimulating the superior cervical ganglion and causing contraction of the nictitating membrane. It caused slowing followed by acceleration of the rate of beat of isolated rabbit atria. The denervated gastrocnemius muscle contracted if dimethylphenylpiperazinium was injected intra-arterially. Under other circumstances a blocking action was seen. It blocked peristalsis in the isolated guinea-pig ileum stimulated by raising intraluminal pressure and inhibited the response of the rat diaphragm and of the cat gastrocnemius stimulated through the motor nerve. It is suggested that dimethylphenylpiperazinium acts by depolarization, causing stimulation of resting muscle but inhibition by prolonging depolarization.

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Effect of 1,1-Dimethyl-4-Phenylpiperazinium Iodide on Peristaltic Reflexes of Isolated Guinea Pig Ileum

Cited by 6 publications

References 0 publications

Effect of Drugs on the Noradrenaline Content of Brain and Peripheral Tissues and Its Significance

Effect of Drugs on the Noradrenaline Content of Brain and Peripheral Tissues and Its Significance

An Analysis of the Blocking Action of Dimethylphenylpiperazinium Iodide on the Inhibition of Isolated Small Intestine Produced by Stimulation of the Sympathetic Nerves

Actions of Dimethylphenylpiperazinium

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