Dopamine Receptor Blocking Activity of Sulpiride in the Central Nervous System

Honda, Fumio; Satoh, Yoshihiko; Shimomura, Kyoichi; Satoh, Hisashi; Noguchi, Hideyo; Uchida, Seiichi; Kato, Ryuichi

doi:10.1254/jjp.27.397

Cited by 91 publications

(18 citation statements)

References 31 publications

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“…The anti-dopamine character of sulpiride in the central nervous system has been described in many reports (1,(17)(18)(19)(20)(21)(22)(23). However, the drug was reported not to block the dopamine-sensitive adenylate cyclase (24,25).…”

Section: Discussionmentioning

confidence: 99%

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Dopamine Receptor Blocking Activity of Sulpiride in the Canine Exocrine Pancreas

Satoh

Honda

1980

Japanese Journal of Pharmacology

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Abstract-The inhibitory effect of sulpiride on dopamine receptors was investigated in the exocrine pancreas of dogs anesthetized with pentobarbital and with the stomach ligated at the pylorus. All test substances were given intravenously. Dopamine, acetylcholine, histamine and secretin produced a dose-related increase in pancreatic juice secretion, though the dose-effect curves of these secretagogues differed in shape. Epinephrine, norepinephrine, isoproterenol, methamphetamine and serotonin had no secretagogue effects. The effects of acetylcholine and histamine were inhibited by atropine and cimetidine, respectively. The effect of dopamine was blocked by halo peridol, but not by atropine, cimetidine, phentolamine and propranolol. These results suggest that dopamine acts on specific dopamine receptors related to the exocrine pancreatic secretion.Haloperidol had no effect on the effects of acetylcholine and histamine, but did inhibit the secretin-induced secretion, though the inhibitory effect was to a lesser extent than on the dopamine response. Sulpiride and chlorpromazine also suppressed dose-dependently the dopamine-induced secretion. The inhibitory activity of sulpiride was almost the same as that of haloperidol, and 12 times more potent than that of chlorpromazine.Sulpiride was found to be a potent dopamine antagonist in the canine exocrine pancreas.In a previous report we showed that sulpiride`, an antipsychotic drug, has essentially a potent inhibition on dopamine receptors in the central nervous system. This drug, when given intraventricularly to rats, was equally or more effective than haloperidol in inducing catalepsy and in inhibiting apomorphine and methamphetamine-induced circling behavior (1). The present paper deals with antagonism of sulpiride to dopamine in the exocrine pancreas of dogs.Hashimoto and collaborators demonstrated that exogenous dopamine increases the secretion of pancreatic juice, of which the components are similar to those induced by exogenous secretin (2), and that there are specific dopamine receptors related to the exocrine pancreatic secretion in dogs (3-6). Thus, the dopamine receptor response can be easily quantified by measuring the increases in volume of the pancreatic juice. This system is a convenient tool for studies on the interaction between dopamine and test substances.We attempted to evaluate the antidoparnine activity of sulpiride, chlorpromazine and haloperidol given to anesthetized dogs before an i.v. administration of dopamine in order to evoke increased pancreatic secretion. We also examined the specificity of the pancreatic dopamine receptor response to dopamine injected systemically, as the dopamine receptor

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Section: Discussionmentioning

confidence: 99%

“…This drug, when given intraventricularly to rats, was equally or more effective than haloperidol in inducing catalepsy and in inhibiting apomorphine and methamphetamine-induced circling behavior (1). The present paper deals with antagonism of sulpiride to dopamine in the exocrine pancreas of dogs.…”

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confidence: 95%

Dopamine Receptor Blocking Activity of Sulpiride in the Canine Exocrine Pancreas

Satoh

Honda

1980

Japanese Journal of Pharmacology

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“…In the literature only a few experiments have been reported which used intracerebral injections of sulpiride to study its effects on particular cerebral mechanisms (Arnt, 1983;Costalletal., 1978;Honda et al, 1977;Nishibe et al, 1982;Woodruff and Andrews, 1979).…”

Section: Introductionmentioning

confidence: 99%

Sulpiride blocks postsynaptic dopamine receptors in the nucleus accumbens

Morgenstern

Fink

1985

J. Neural Transmission

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Intra-accumbens injection of sulpiride, tiapride, and metoclopramide antagonized locomotor hyperactivity induced by intraperitoneal administration of apomorphine in rats and measured over the first five minutes after introducing the animal to an open-field cage. Sulpiride was slightly more potent than tiapride which was more than 10 times more potent than metoclopramide and haloperidol. The threshold dose of sulpiride was as low as 0.001 microgram, bilaterally. Intra-accumbens injection of sulpiride also blocked exploratory hypermotility induced by bilateral intra-accumbens injections of apomorphine and picrotoxin. The threshold dose of sulpiride for blocking these two effects was about 0.01 microgram, bilaterally. Sulpiride was more than 10 times more potent than haloperidol in blocking this apomorphine-induced hypermotility. Haloperidol did not influence the picrotoxin hypermotility. The results obtained indicate strong postsynaptic dopamine antagonist properties of sulpiride, tiapride and metoclopramide.

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“…However, drugs used so far, i.e., dopamine (DA) precursor or agonist drugs as L-dopa or bromocriptine or DA receptor blockers, such as chlorpromazine, metoclopramide and sulpiride, have not fulfilled the above re quirement [5,7], Although other interpretations cannot be eliminated, the lack of discriminating ability of the DA blockers is probably because they demand the integrity of both CNS and pituitary for their PRL-releasing effect [1,10], The availability of DA receptor blockers which do not cross the blood-brain barrier (BBB), and therefore exert their action only at 'peripheral' DA receptors, should provide a neuropharmacologic means capable of better differentiating between organic and 'functional' cases of enhanced PRL secretion.…”

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Prolactin-Releasing Effect of Domperidone in Normoprolactinemic and Hyperprolactinemic Subjects

Camanni¹,

Genazzani²,

Massara³

et al. 1980

Neuroendocrinology

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The prolactin (PRL)-releasing effect of domperidone (DOM), a novel antidopaminergic drug which does not cross the blood-brain barrier, was investigated in normoprolactinemic subjects, in subjects with physiologic puerperal hyperprolactinemia or pathological hyperprolactinemia. DOM (4 mg i.v.), administered to 8 normoprolactinemic women, induced a clear-cut and sustained rise in plasma PRL, with peak levels occurring 15–30 min postinjection; the effect of the drug was also evident in 3 normoprolactinemic women at the dose of 0.25 mg i.v. Also in 8 puerperal women (postpartum day 2) intravenous administration of 4 mg DOM was followed by an increase in plasma PRL (51–517% of baseline levels, 15–45 min postinjection). Administration of DOM (4 mg i.v.) to 16 subjects with pathological hyperprolactinemia, evidenced the presence of 14 DOM-nonresponder (maximum percent increase of baseline PRL 48%) and 2 DOM-responder subjects. In 8 of the DOM-nonresponder subjects the existence of a pituitary tumor was established at surgery by selective removal of an adenoma (7 subjects) or a teratoma (1 subject): of the 6 subjects who did not undergo surgery, 3 had biochemical and/or radiologic evidence suggestive of a PRL-secreting tumor and 1 was acromegalic. These results indicate that DOM is capable of releasing PRL both in normoprolactinemic subjects and subjects with puerperal hyperprolactinemia. In contrast, DOM is unable to modify PRL levels in most of subjects with pathological hyperprolactinemia, with proven or suspected pituitary tumors.

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Dopamine Receptor Blocking Activity of Sulpiride in the Central Nervous System

Cited by 91 publications

References 31 publications

Dopamine Receptor Blocking Activity of Sulpiride in the Canine Exocrine Pancreas

Dopamine Receptor Blocking Activity of Sulpiride in the Canine Exocrine Pancreas

Sulpiride blocks postsynaptic dopamine receptors in the nucleus accumbens

Prolactin-Releasing Effect of Domperidone in Normoprolactinemic and Hyperprolactinemic Subjects

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