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PubMed1980

Comparative studies of prolactin secretion in estradiol-primed and normal male rats induced by ether stress, pimozide and TRH.

The differences in plasma prolactin concentration between normal and estradiol-implanted male rats were compared after treatment with 3 different stimulating agents of prolactin secretion [ether anesthesia, pimozide (a "specific' dopaminergic receptor blocking agent) and TRH] using conscious, free-moving rats implanted with permanent intra-atrial cannulae. It has recently been shown that ether stress raises the circulating prolactin concentration by stimulating PRF secretion. The ether stress elevated prolactin concentration from 100 to 400 ng/ml in the estradiol-implanted rat and from 10 to 40 ng/ml in the normal male. Thus, the ether stress elevated the prolactin concentration 4 times over the basal level in both normal male and estradiol-implanted male rats, implying that the physiological role of the PRF is not changed by the estradiol implantation. A bolus injection of pimozide (1 mg/kg) elevated the plasma prolactin concentration in both the normal and estradiol-implanted male with an initial surge followed by descent to a maintained plateau level. This plateau level in the estradiol-primed rat was 600 ng/ml and in the nonprimed male rat, 50 ng/ml. The ratio of the plateau concentration over the basal level was 4 times for both groups, suggesting that the physiological role of the PIF in the estradiol-implanted rat is not different from that in the normal male rat. It is known that TRH not only stimulates TSH secretion but will stimulate prolactin secretion as well. A very large dose (0.6 mg/kg) of TRH elevated prolactin concentration 6-fold in the estradiol-implanted rat but stimulate little prolactin secretion in the normal male rat. Since ether exposure appears to stimulate prolactin secretion in both estradiol-primed and non-primed male rats through PRF secretion, while TRH was not able to stimulate a significant amount of prolactin secretion in the normal male rat, we concluded that TRH acts to stimulate prolactin secretion in estradiol-primed rats but through a different mechanism than that operating for PRF.

Animals↗
PubMed1976

Application of the neuroleptic pimozide (ORAP-R 6238) for tranquilizer indications in a controlled study.

The effect of the neuroleptic pimozide at doses of 2 mg/day was compared with that of diazepam at doses of 3 x 5 mg. This double-blind study involved 50 outpatients with psychovegetative syndromes and anxiety neuroses. At these doses and under the described test conditions both preparations were virtually equally effective. Pimozide can therefore be considered an alternative preparation for 'genuine' tranquilizers. Above all, its application seems to be useful in patients that are prone to drug abuse, and therefore, a priori, endangered by habit formation.

Adult↗
PubMed1981

The effect of pimozide on CSF norepinephrine in schizophrenia.

The authors measured CSF norepinephrine concentrations in drug-free schizophrenic patients with and without probenecid administration and in drug-free normal control subjects. Schizophrenic patients had significantly higher baseline norepinephrine values. The dopamine metabolite homovanillic acid correlated significantly with norepinephrine. During chronic treatment with the neuroleptic pimozide, patients' norepinephrine levels were significantly decreased. The pimozide-induced decrease in norepinephrine, as well as the percent decrease, correlated significantly with the patients' decrease in global psychosis. These data are consistent with recent reports of elevated concentrations of norepinephrine in specific brain areas of schizophrenic patients, and they support a role for norepinephrine metabolism in the pharmacological effects of antipsychotic drugs.

Adolescent↗
PubMed1983

Treatment of Gilles de la Tourette syndrome with pimozide.

The results of this clinical study of 31 patients with Tourette syndrome suggest that pimozide is more effective and induces fewer side effects than haloperidol in some patients. The clinical advantages of pimozide may be associated with its more specific dopamine-blocking properties and the absence of significant norepinephrine effects. The authors recommend further controlled study of exclusive dopamine antagonists in the treatment of Tourette syndrome.

Adolescent↗
PubMed1978

Token economy, pimozide and chronic schizophrenia.

Response to a token economy was assessed in male chronic schizophrenic in-patients who were given, in a double-blind cross-over trial, pimozide (up to 20 mg daily) or chlorpromazine )up to 1,000 mg daily), each for three months. After six months there was little change in the patients' mental state, but general ward behaviour and token-rewarded "target" behaviours improved significantly. There were no statistically significant between-drug differences, but the trend was that general ward behaviour, but not token-rewarded behaviour, improved more on pimozide. The patients who showed initiative and cooperated best with staff were those whose token-rewarded behaviour was most satisfactory.

Behavior Therapy↗
PubMed1989

Pimozide in pathological jealousy.

A 39-year-old man had his pathological jealousy successfully treated with pimozide. It is suggested that pimozide might be considered the drug of choice in all the monodelusional disorders.

Adult↗
PubMed1978

In vitro effect of dopamine and pimozide on human chorionic somatomammotropin (hCS) secretion.

In human placental explants cultured in vitro, dopamine inhibited human chorionic somatomammotropin (hCS) secretion into the culture media. In the control flasks, the level of hCS secretion was 130.5 +/- 7.8 micrograms/g tissue (n = 6). When 1 mM dopamine was added, hCS levels decreased to 80.2 +/- 11.5 micrograms/g tissue (P less than 0.01). Dopamine (5 and 10 mM) further lowered hCS levels. In contrast, 1 mM pimozide enhanced hCS secretion by 2-fold as compared to control levels (248.2 +/- 44.8 vs. 130.5 +/- 7.8, P less than 0.02). The simultaneous addition of dopamine did not alter the stimulatory effect of pimozide on hCS secretion. In separate experiments, arginine (1 and 5 mM) and somatostatin (1 microgram/ml culture media) did not alter hCS secretion from placental explants. These results suggest that hCS secretion is modulated by dopaminergic receptors.

Arginine↗
PubMed1979

The effect of methysergide, pimozide, and sodium valproate on the diazepam-stimulated growth hormone secretion in man.

Diazepam-induced GH secretion was tested on 28 male volunteers before and after a 3-day treatment with methysergide, pimozide, or sodium valproate. Serum GH, diazepam, and blood glucose levels were determined. Without prior medication, the mean serum GH level increased 336% 1 h after diazepam administration. Treatment with the serotonin antagonist, methysergide, had no effect on the diazepam-stimulated GH secretion, whereas pimozide, the selective dopamine receptor-blocking agent, reduced the GH response to diazepam by 50% (P less than 0.05). Sodium valproate, a gamma-aminobutyric acid transaminase inhibitor, also inhibited diazepam-induced GH secretion; stimulated GH levels were 51% at 30 min (P less than 0.025), 39% at 60 min (P less than 0.025), and 46% at 90 min (P less than 0.025) relative to the stimulated levels without medication. No difference was found in blood glucose or serum diazepam levels after the drug treatments relative to the values obtained under basal conditions. It is suggested that diazepam-induced GH secretion is at least partly mediated via dopaminergic mechanisms. Serotonin does not seem to be involved. It is further proposed that gamma-aminobutyric acid plays an inhibitory role in GH secretion.

Adult↗
PubMed1977

Stimulating action of sulpiride and pimozide on prolactin release. Effect on bromocriptine, L-dopa and metergoline administration.

In order to evaluate the mechanism of action of metergoline, an antiserotonin agent, the effect of pre-treatment with metergoline on prolactin (PRL) release induced by sulpiride was compared to that obtained after bromocriptine administration in normal subjects. In addition, the metergoline effect on PRL release induced by pimozide, specific dopamine receptor blocking agent, was compared to that obtained with L-dopa. Metergoline administration resulted in definite decrease in plasma PRL in all subjects; however, metergoline did not block, differently from bromocriptine, the PRL release induced by sulpiride. On the contrary, metergoline, like L-dopa, inhibited PRL release induced by pimozide pre-treatment. These results raise the possibility that metergoline does not act as an antiserotonin agent; its antilactogenic effect observed under basal conditions may be dependent on different mechanisms of action.

Adolescent↗
PubMed1979

Effect of pimozide on the response of LH-RH in intact adult male rats.

The effect of Pimozide on serum and pituitary concentration of LH was studied in adult male intact rats. Also the release of LH under stimulation of exogenous LH-RH was measured. The treatment for 5 days with pimozide did not alter the serum LH levels, decreased the release of LH by exogenous LH-RH stimulation, and increased the pituitary LH concentration. These results would indicate that blocking the dopaminergic receptors alters pituitary LH release mechanism.

Animals↗
PubMed1975

The effects of dexetimide on pimozide-, haloperidol- and pipamperone-induced inhibition of brain self-stimulation in rats.

Pimozide (0.04, 0.16, 0.63 and 2.50 mg/kg), haloperidol (0.01, 0.04, 0.16 and 0.63 mg/kg) and pipamperone (2.50, 10.0, 40.0 and 160 mg/kg) were given subcutaneously to rats, pressing a lever for brain-stimulation through electrodes implanted in the lateral hypothalamic region of the medial forebrain bundle. The lowest dose of each neuroleptic did not affect self-stimulation; the second dose inhibited the response rate by approximately 50%, whereas the two highest doses completely suppressed self-stimulation behaviour. The centrally acting anticholinergic dexetimide (0.63 mg/kg, s.c.) completly antagonized the pimozide-induced inhibition; the haloperidol-induced inhibition was also completely antagonized except at its highest doses, whereas the effects of the sedative neuroleptic pipamperone were not antagonized. These data are consistent with a presumed dopaminergic cholinergic striatal interaction and show brain self-stimulation to be an effective measure of neuroleptic-anticholinergic interaction.

Animals↗
PubMed1992

Pimozide in autistic children.

This open pilot study explored the efficacy and safety of pimozide, over a 3-week period, in hospitalized autistic children. Eight males, ages 4.2 to 8.3 years, completed the study. Intellectual functioning ranged from moderate to profound mental retardation. Symptoms included severe withdrawal, stereotypies, hyperactivity and/or hypoactivity, aggressiveness, and temper tantrums. Therapeutic daily doses of pimozide ranged from 3.0 mg to 6.0 mg with a mean of 4.9 mg (0.12-0.32 mg/kg; mean, 0.22). Laboratory studies including electrocardiogram and liver function tests remained within normal limits. Untoward effects were minimal and transient. Decreases of behavioral symptoms were evidenced on all measures including the Children's Psychiatric Rating Scale, Clinical Global Impressions, and Global Clinical Judgments Scale (consensus rating). Of the 5 hypoactive children, 4 showed a decrease in hypoactivity, whereas 1 child showed worsening. These findings are promising and indicate the need for further study.

Autistic Disorder↗
PubMed1991

The role of pimozide in clinical psychiatry: a review.

Pimozide, a diphenylbutylpiperidine neuroleptic which is FDA-approved as a backup treatment for Gilles de la Tourette's syndrome, has been used abroad for many years as a treatment of schizophrenia and has been recently reported to be particularly effective in treating monosymptomatic hypochondriacal psychosis and delusional jealousy. Pimozide may also have a role in the treatment of negative schizophrenic symptoms, pain syndromes, and obsessive compulsive disorder. After reviewing the relevant clinical literature supporting these indications, the authors review preclinical studies that provide points of departure regarding biochemical mechanisms underlying this unique therapeutic profile.

Chronic Disease↗
PubMed1988

Definite and sustained improvement with pimozide of two patients with severe trigeminal neuralgia. Some neurochemical, neurophysiological and neuroendocrinological findings.

In the present study we report two typical cases of trigeminal neuralgia in whom all conventional drug treatments were attempted without success, and in whom low doses of pimozide, a dopaminergic blocking agent, provoked a definite and sustained improvement. All biological markers used in these cases provided indirect evidence that a central serotonergic hypoactivity is an underlying mechanism in this disease. A low intestinal tone, raised levels of norepinephrine, dopamine, platelet serotonin and non-platelet plasma serotonin were registered during relapses and normalized during improvement periods. Pimozide was not able to improve the depressive state diagnosed in these two cases, nor in 13 other trigeminal neuralgia patients (not reported in this study).

Aged↗
PubMed1978

The observer interaction variable in evaluation of socialising properties of pimozide (Orap).

Eighteen chronic, institutionalised patients were randomly assigned to two groups for the purpose of a double blind trial of pimozide (Orap). The results of the study indicated an increase in socialisation, as measured by the Venables scale, for both groups, and no significant difference in this variable between placebo and active preparation groups. It is suggested that greater observer interaction may be responsible for the observed increase in socialisation previously attributed to pimozide.

Clinical Trials as Topic↗
PubMed1985

Effects of pimozide and domperidone administration on prolactin levels in neonatally estrogenized female rats.

The effects of two dopaminergic blockers, pimozide and domperidone, on the prolactin secretion were investigated in adult female rats treated neonatally with estrogens (100 micrograms of estradiol benzoate s.c. on day 1). These rats showed hyperprolactinemia (556 micrograms/l vs 57.7 in oil-injected) and treatment with pimozide or domperidone failed to increase prolactin levels in the adult age. These results suggest that the hyperprolactinemia in neonatally estrogenized female rats is produced by loss of the dopaminergic inhibition on prolactin secretion, so that the pharmacological blockade of dopaminergic receptors is uneffective. The dopamine levels in hypothalamus were similar in control and estrogenized females suggesting that failure in dopaminergic inhibition is due to a decrease in dopamine secretion to portal vessels.

Animals↗
PubMed1979

Failure of phenoxybenzamine and pimozide to diminish changes in oxygen consumption and body temperature produced by caffeine.

The effects of a dopamine antagonist (pimozide) and an alpha-adrenergic receptor blocking agent (phenoxybenzamine) on caffeine-induced changes in oxygen consumption. body temperature, blood glucose and non-esterified fatty acids (NEFA) were studied in mice. Both drugs had no effect on the increase of the oxygen consumption produced by caffeine. The decline of the body temperature induced by caffeine was not significantly influenced by pimozide, while phenoxybenzamine accentuated the hypothermic effect of caffeine. The results indicate that alpha-adrenergic and dopamine receptors do not play an essential role in the caffeine-induced stimulation of overall metabolism and hypothermia.

Animals↗
PubMed1983

[Potentiation by pimozide of the effects of LHRH-A on hypophyseal gonadotropin secretion, ovulation and spermiation in the common carp (Cyprinus carpio)].

During the reproductive season in August, we administered to adult male and female Carp an LHRH analog (LHRH-A = D-trp6EA-LHRH) (50 micrograms/kg) alone or in association with pimozide, a dopamine inhibitor (10 mg/kg). LHRH-A caused the circulating portal level of gonadotropin to rise significantly in males and less in females. Spermiation was stimulated in the males and oocyte maturation in females but there was no ovulation. An infection of pimozide and then of LHRH-A 6 h later significantly increased c-GTH secretion and spermiation more than LHRH-A given alone, and induced ovulation in the females.

Animals↗