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SOME PHARMACOLOGICAL PROPERTIES OF THIOPROPERAZINE AND THEIR MODIFICATION BY ANTI-PARKINSONIAN DRUGS.

The pharmacological properties of a phenothiazine derivative thioproperazine have been compared with those of chlorpromazine, and the modifications by some anti-Parkinsonian drugs of its actions on the central nervous system have been studied. Thioproperazine was less potent than chlorpromazine in lowering blood pressure and antagonizing adrenaline in the cat, in depressing respiratory rate in the rabbit, in producing hypothermia and analgesia and in reducing the minimum anaesthetic dose of hexobarbitone in mice, and in protecting rats from convulsions induced by tryptamine. It was roughly equipotent to chlorpromazine in reducing locomotor activity of mice. Thioproperazine was more potent than chlorpromazine in protecting grouped mice from the acute toxicity of dexamphetamine, in preventing the acute behavioural disturbances produced by dexamphetamine in the rat, in producing a state of experimental catatonia in the rat and in preventing the emetic action of apomorphine in the dog. Hyoscine, benztropine or promethazine greatly reduced the ability of thioproperazine to prevent behavioural changes due to dexamphetamine in the rat and also abolished symptoms of experimental catatonia produced by thioproperazine. In contrast, the antiapomorphine activity of thioproperazine in the dog was not reduced to any extent by hyoscine or benztropine.

Anesthetics↗

[Changes in plasma prolactin and magnesium in male rats treated with thioproperazine and/or bromocriptine].

The Ca2+ dependent release of both dopamine (DA) and prolactin (Prl) is modified by stress. Plasma magnesium (Mg) concentrations are also modified. Therefore, we have investigated on plasma (P) Mg and Prl, the immediate and delayed effects of one, five or six daily injections of bromocriptine (BMC, 200 micrograms/100 g) and thioproperazine (100 micrograms/100 g), respectively agonist and antagonist of pituitary DA receptors. One hour after injection of either drugs, an increased P Mg is observed while P Prl is increased or decreased. No correlation is, thus, established between P Prl and P Mg changes. The P Mg increase is long-lasting after BMC, transitory after thioproperazine as shown by determinations performed 23 h after the 5th injection. When the two drugs are simultaneously given, no important modifications of P Mg are observed. The mechanisms and consequences of this P Mg increase are discussed. During stress, the hypermagnesemia could modulate the Prl secretion and action, hindering its secretion on one hand, and potentiating its action on target-organs, on the other hand.

Animals↗

[Inhibition of nidation in mice by modification of the environment and pheromones. Re-establishment by prolactin and thioproperazine].

325 mated mice (evidence of a vaginal plug, J1) were divided into 8 groups, 246 were subjected to various kinds of stress before day 7 of gestation: 120 were placed singly in boxes and/or transferred to different ones: 75 were exposed to alien males with or without box transfer. 85% of the 50 unstressed females did, in fact, become pregnant. Isolation by itself did not modify the course of gestation. Transfer to a new box (74 females) along with isolation from days, 1, 2, 3 or 4 on reduced the percentage of pregnant females to 55%. Exposure to a strange male in the common box of females (26 females) reduced it to 55%. Isolation of a single female with a strange male, along with transfer (49 females; Bruce Effect) on day 4, 5 or 6 reduced this percentage to 25, 6 or 20% respectively. In addition when the stress occurred on day 4 the number of implantations was greatly reduced. A daily s. c. injection of B prolactin or of thioproperazine on days 4, 5 and 6 prevented the onset of the pregnancy block (47 females). If the 325 mice are separated into 2 groups, those ind whom gestation was maintained and those who aborted, ponderal growth greatly increased in the former; their adrenal glands weighed less, and their preputial glands weighed more. An excessive secretion of corticosteroids in non-pregnant females could be the cause of the inhibition of prolactin release. These results suggest that the effects and probably the implicated mechanisms are the same for pheromones and environmental changes as prolactin and thioproperazine prevent the effects in both cases. The variation in the susceptibility of mice could be due to genetic factors that play a primary role in hypophyso-adrenal response to emotional stress.

Animals↗

Effects of thioproperazine and sulpiride on the locomotor rhythms in the decorticate cat.

The decorticate cat develops sequences of locomotor movements, especially in the two posterior limbs: those appear either spontaneously, or following a single shock applied to L7 dorsal root. Using this preparation, we tested the effects of two neuroleptic agents, Thioproperazine (TZ) and Sulpiride (S), through either systemic administration or local injection into the lateral-posterior hypothalamus and into the lumbar spinal cord. TZ administered i.v. (0.5 mg/kg) suppressed all locomotor rhythms, while S induced unclear effects. The tested drugs clearly acted at the hypothalamic level, but the effects of the drugs were opposite; TZ (70 microgram) suppressed rhythms, while S (350 microgram) increased or even induced them. T2 (50 microgram) injected at the L7 cord-level abolished rhythms, and S (350 microgram) reduced their amplitude but increased the duration of locomotor sequences. The flexion reflex was never affected by these drugs. The two drugs seem to act at the spinal and the hypothalamic levels. The possible mechanisms involved in their action are discussed.

Animals↗

Treatment of ulcerative colitis with thioproperazine.

Thioproperazine, an antipsychotic drug, dramatically improved three ulcerative colitis (UC) patients. We tried this dopaminergic blocking agent in patients with UC because Tp (but not other neuroleptics) suppressed the motility of the distal colon in one patient. All three patients showed impressive improvement by clinical, radiological, endoscopic, histological, and biochemical measures. Although peripheral mechanisms cannot be discarded, we postulate that centrally induced effects offer more satisfactory explanation for the drug's apparent benefit. The fact that Tp, but not other phenothiazine derivatives, penetrate some brain dopaminergic areas could explain Tp's particular effect. We caution that this is a preliminary observation and one that needs confirmation by controlled clinical trials.

Adolescent↗

[Comparative study using double-blind method of sultopride and thioproperazine].

This report includes a statistical analysis of the results of a double blind comparative study between sultopride and thioproperazine. Two rating scales were used: the standard B.P.R.S. and a simplified scale including 7 items: agitation--delusion--thought-disorganization--anxiety--aggressivity--hallucinations--autism. The comparison of the mean of the global scores obtained with the two rating scales shows a significant difference in activity in favour of sultopride. The analysis of the individual items shows regular modifications in favour of sultopride but these are not statistically significant. There are, also, no differences in the side-effects observed, particularly extra-pyramidal effects.

Antipsychotic Agents↗

On the use of clonidine and thioproperazine in a woman with Gilles de la Tourette's disease.

A 25-year-old woman with Gilles de la Tourette's disease was successfully treated with clonidine (an inhibitor of noradrenaline release). However, the drug was stopped because of side effects. Thioproperazine, a phenothiazine derivative which blocks subcortical dopaminergic receptors, suppressed Gilles de la Tourette's symptoms totally. The patient has tolerated the drug well for over a year since its introduction. The pharmacomanometric investigation performed in this patient showed hyperactivity of her noradrenergic system.

Adult↗