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At least 19 recordsLinked to original sources
PubMed1990

Differential modulation of mouse brain biogenic amines by haloperidol and pimozide: implications in Tourette's syndrome.

1. A comparison between the effect of equal dose regimens of Tourette's medications on mouse motor activity and regional brain monoamines suggests differential responses which may underlie drug-induced side-effects. 2. Haloperidol was more potent than pimozide in altering striatal dopamine concentration which may account for the greater incidence of haloperidol-induced extrapyramidal disorders compared to pimozide. 3. Pimozide, but not the haloperidol treatment, altered brain serotonin concentrations to suggest a decrease in turnover rate which may underlie pimozide-caused sedation in Tourette's syndrome. 4. Pimozide was more potent than haloperidol in duration of behavioral depression which suggests differential dopamine receptor subtypes blockade. 5. Pimozide was more potent than haloperidol in altering 3 of the 6 brain regions content of norepinephrine-derived normetanephrine which may be responsible for the increase in blood pressure reported during pimozide treatment.

Animals↗
PubMed1992

Effects of cocaine and pimozide on plasma and brain alpha-melanocyte-stimulating hormone levels in rats.

The effects of cocaine on rat plasma and brain alpha-melanocyte-stimulating hormone (alpha-MSH) levels have been studied by means of a specific radioimmunoassay. The selected brain areas were the hypothalamus, septum-nucleus accumbens and hippocampus. Cocaine given subcutaneously decreased the alpha-MSH levels in the peripheral blood. Pimozide, a dopaminergic antagonist, had an opposite effect: it increased the alpha-MSH levels in the peripheral blood. Combined treatment with cocaine + pimozide resulted in a decrease in the pimozide-induced increase in alpha-MSH levels in the blood. Cocaine and pimozide or the combination of cocaine + pimozide were ineffective on the alpha-MSH levels in the hypothalamus and septum-accumbens brain regions. In the hippocampus, cocaine in the dose applied induced a slight but not significant decrease in the alpha-MSH level. Pimozide caused a significant decrease in the hippocampal alpha-MSH level which disappeared at 60 min. Cocaine prevented the pimozide-induced depletion of alpha-MSH. The data indicate that cocaine may act as a dopaminergic agonist in the mechanism of control of alpha-MSH secretion from the intermediate lobe of the pituitary. The alpha-MSH levels in the brain are controlled by different mechanisms. In some brain areas, the dopaminergic system has no action; in others the mechanisms might be similar to but slightly different from that in the pituitary.

Animals↗
PubMed1977

Effects of pimozide on the acquisition, maintenance, and extinction of an amphetamine-induced taste aversion.

Different groups of rats were pretreated with the dopamine receptor blocker, pimozide (0.25, 0.5, or 1.0 mg/kg), in an attempt to investigate the role of dopaminergic transmission in the acquisition, maintenance, and extinction of a taste aversion produced by d-amphetamine dulphate (1.0 or 2.0 mg/kg). In the first phase of the experiment, all doses of pimozide attenuated but did not block the acquisition of the aversion produced by 1.0 mg/kg but not by 2.0 mg/kg amphetamine. In Phase II, pimozide pretreatment was suspended to allow the attenuated groups to acquire the aversion and then reintroduced in Phase III. In this phase all groups continued to avoid the taste, indicating a failure of pimozide to affect the maintenance of the avoidance response. When amphetamine treatment was suspended in Phase IV, pimozide accelerated the extinction, especially in those groups that had previously received the 1.0 mg/kg dose of amphetamine. These results are discussed with reference to dopaminergic mechanisms in avoidance learning and a pimozide-mediated reduction in the functional strength of amphetamine as an unconditioned stimulus.

Animals↗
PubMed1976

Pimozide: a review of its pharmacological properties and therapeutic uses in psychiatry.

Pimozide 1-(1-[4,4-bis(4-fluorophenyl)butyl]-4-peperidinyl)-2-benzimidazolone, is the first of a new series of psychotropic drugs, the kiphenylbutylpiperidines. It is advocated for once-daily use as maintenance therapy in chronic schizophrenia and for the treatment of psychic and functional disorders induced by personality traits. Published data suggest that in chronic schizophrenia, pimozide 4 to 6mg daily is indistinguishable from maintenance doses of chlorpromazine, fluphenazine, flupenthixol, perphenazine, or thioidazine. Patient groups have usually been to small to allow statistically significant differences to be apparent, but in some trials pimozide was significantly superior to trifluoperzine and to haloperidol. On present evidence, pimozide has no place in the hyperactive, aggressive type of patient or in treating the acute phase of schizophrenia, probably because of its relative lack of sedative properties compared with many antipsychotic drugs. The incidence and severity of extrapyramidal reactions with pimozide are low, but suitably designed controlled studies are needed to determine whether its use leads to a reduction in the requirement for antiparkinsonian medication. In anxious patients, pimozide seems to offer no advantages over currently available anxiolytic agents, either in terms of efficacy or incidence of side-effects. Claims for a specific effect against anxiety associated with psychosis or disturbed personality traits remain unproven.

Adult↗
PubMed1976

Clinical trial of pimozide.

Pimozide and Chlorpromazine were compared in chronic schizophrenics for their therapeutic effectiveness and tolerance, for four-weeks in both cases and for twelve months for pimozide. The minimum and maximum doses were 1 mg to 4 mg single dose for pimozide and 100 to 200 mg thrice daily for chlorpromazine. No significant global differences between the range of therapeutic activity of the two regimens were observed. Slightly more improvement was observed in mood and motor activity with pimozide. Drowsiness and dizziness, and extrapyramidal effects were more prominent with clorpromazine. Other side effects were infrequent. A prolonged improvement in 8 pimozide patients was maintained with mainly weight gain. The advantages of pimozide in chronic unsocialized schizophrenics appear to rest on its single oral daily dose regime, minimal undersirable effects, its specific enhancement of social integration and absence of undersirable effect on mental and physical performance.

Adolescent↗
PubMed1978

Effect of pimozide on the cytology of the eel pituitary. I. Prolactin-secreting cells.

Pimozide, a specific blocker of dopaminergic receptors, was injected for 4 to 9 days in freshwater (FW) eels or eels acclimated to sea water (SW), for 10 to 30 days. The daily dose was 100 or 200 microgram/100 g. In FW, pimozide induces a nuclear hypertrophy in the prolactin (PRL) cells of eels; these elongated cells increase in height. The amount of erythrosinophilic granules in the cytoplasm, initially reduced, increases. Plasma electrolyte values are not modified: only the plasma sodium level slightly rises with the higher dose. In SW, PRL cells appear less active. After 10 days, this hypoactivity is not yet fully evident; pimozide stimulates PRL cells without affecting electrolyte values. After 1 month in SW, PRL cells are stimulated with pimozide and a slight regranulation may occasionally occur. The response in SW is never as marked as it is in FW; a high dose is not more effective than a low one. The higher dose significantly raises Na+, Ca2+ and Cl- plasma levels. These data suggest that prolactin synthesis and release increase with pimozide. They corroborate the hypothesis of a hypothalamic inhibitory control on PRL secretion mediated through dopaminergic fibers in the eel, but other factors may also be involved in this regulation in addition to the effect of salinity.

Animals↗
PubMed1977

Effects of pimozide on noradrenergic transmission in rabbit isolated ear arteries.

In the rabbit ear artery both dopamine and noradrenaline inhibit stimulation-induced (S-I) transmitter noradrenaline efflux. Pimozide, which is reported to be a specific dopamine receptor antagonist, was used to further study the effects of dopamine on transmitter efflux. In a concentration of 0.2 micrometer pimozide blocked the inhibition of S-I efflux produced by 0.5 micrometer dopamine but not that produced by 0.5 micrometer noradrenaline. In a concentration of 10 nM, pimozide enhances transmitter release and vasoconstrictor responses to sympathetic nerve stimulation; this may be due to blockade of feedback inhibition of transmitter release by endogenous dopamine. In a concentration of 1 micrometer, pimozide reduced transmitter release and vasoconstrictor responses to sympathetic nerve stimulation. Vasoconstrictor responses to noradrenaline and histamine are antagonized by pimozide in a noncompetitive manner.

Animals↗
PubMed1992

Influence of pimozide on a TRH induced TSH secretion in the rat during food deprivation.

Adult Wistar rats food deprived for 3 days had lower basal levels of TSH compared to normal fed animals. An increase of these lower levels to normal values was obtained following a prolonged (injections during 3 consecutive days) or acute treatment (single injection) with pimozide (1 mg/injection). Blood samples obtained after the last or an only injection of pimozide contained profound increased prolactin levels. Prolactin increase was more than 100-fold in fed and more than 30-fold in starved rats following prolonged pimozide treatment and more than 25-fold and 10-fold following a single injection of pimozide. An injection of 250 ng of TRH increased plasma concentrations of TSH in all groups, but this increase was more pronounced in fasted rats injected with pimozide during 3 consecutive days. It is concluded that fasting results in a dopaminergic inhibition of the sensitivity of the thyrotrophs to a TRH challenge.

Animals↗
PubMed1976

Effect of the dopamine receptor blocking agent pimozide on the growth hormone response to arginine and exercise and on the spontaneous growth hormone fluctuations.

Pimozide, a specific blocker of dopamine receptors, was administered orally to 10 diabetics for 2 days before an arginine-hydrochloride infusion. In 8 healthy volunteers and 20 diabetics exercise tests on a bicycle ergometer were performed with a load of 100 Watts and 50 Watts respectively without or after a single dose of pimozide 30 min before the test. In 4 male diabetics day profiles of growth hormone (GH) were estimated without and during treatment with pimozide for 4 days. The arginine and exercise induced GH release was found to be significantly lowered by pimozide, whereas the marked spontaneous fluctuations in the diabetics were even enhanced by pimozide. These data support the concept of the involvement of dopaminergic stimulation in the response of GH to arginine and exercise. The spontaneous fluctuations of GH, however, seem to be regulated by other neuroendocrine mechanisms.

Adolescent↗
PubMedDate not supplied

Serum and pituitary prolactin variations under the influence of pyridoxine and pimozide in the male rat.

Prolactin was measured in the serum and hypophyses of the male rat after six days of i.p. administration of pyridoxine 5 mg (group B6), after a single dose of pimozide 2.5 mg/kg body (group PMZ), six days of pyridoxine and one dose of pimozide (group B6- PMZ) and a single dose of tartaric acid (controls). Both pyridoxine and pimozide increased the serum prolactin: 59.06 +/- 16.23 ng/ml and 68.45 +/- 10.78 ng/ml respectively (X +/- DS) by comparison to controls: 33.12 +/- 11.16 ng/ml, their effect being cumulative (83.75 +/- 13.86 ng/ml). However, the effect of pyridoxine and pimozide at the central level is different, pyridoxine producing an increase of the pituitary concentration of prolactin, while pimozide depleted the stored prolactin. Hypothetical mechanisms of pyridoxine action at the pituitary level are discussed.

Animals↗
PubMed1976

Non-selective enhancement of locus coeruleus and substantia nigra self-stimulation after termination of chronic dopaminergic receptor blockade with pimozide in rats.

Self-stimulation of substantia nigra and locus coeruleus were assessed before and after an 8-day regimen in which pimozide was given twice daily at a dose of 0.5 mg/kg (first 4 days) or 1.0 mg/kg (last 4 days). At 48 hours after termination of pimozide treatment self-stimulation was increased to 25% above pre-pimozide baseline levels: this was true for both self-stimulation sites. Rates remained high the following day but returned to normal by the third day of post-pimozide-testing. These data are interpreted as reflecting pimozide-induced supersensitivity in a dopamenergic substrate. This substrate appears to be critical for intracranial self-stimulation even when its fibers are not themselves activated at the tip of the stimulating electrode.

Animals↗
PubMed1979

Effects of pimozide on the ultrastructure of the pars distalis in the rat.

The effects of pimozide, a dopamine receptor-blocking agent, were studied in the pars distalis of the rat. The animals received 100 micrograms/100 g pimozide daily for 5, 10, 15, and 20 days. Pimozide induces striking ultrastructural changes after 5 days of treatment. The number of luteotroph (LTH) cells is signficantly increased; they display characteristics of stimulation. The extrusion of granules into the intercellular space via exocytosis is frequently observed. The intercellular spaces are highly dilated, forming a lacunar system filled with an amorphous material, erythrocytes and involuted LTH cells. Transitional stages in the process of involution are observed in LTH cells. Luteotroph cells also form a syncytium. Twenty days after treatment the above-described changes decrease in magnitude. The present findings suggest that pimozide stimulates the mechanism of synthesis and release in the luteotroph cells, an effect that is less evident with longer treatment.

Animals↗
PubMed1992

Pimozide mitigates excessive running in the activity-stress paradigm.

The present study investigated the role of dopamine in the maintenance of behaviors observed in the activity-stress paradigm. In Experiment 1, several doses (0, 0.125, 0.25, 0.50, and 1.0 mg/kg) of the dopamine D2-receptor blocker, pimozide, were administered to rats maintained on an ad lib feeding schedule. Results indicated that 0.25 mg/kg pimozide did not disrupt running activity when compared to control animals. In Experiment 2, injections of either 0, 0.25, or 0.50 mg/kg pimozide were given every 12 hours to rats subjected to the activity-stress paradigm. Although 0.25 mg/kg pimozide had no effect on dark-phase activity, it significantly suppressed light-phase activity and subsequently increased the number of survivors in the paradigm. It was concluded that dopamine plays a role in maintaining high running levels in the activity-stress paradigm.

Animals↗
PubMed1990

Pimozide prevents the response-reinstating effects of water reinforcement in rats.

Thirsty animals were trained to traverse a straight runway once each day for a reward consisting of 100 licks from a water-filled drinking tube. Once running speeds had stabilized, single daily extinction trials were initiated during which no water reinforcement was provided in the goal box. Extinction trials continued until running had slowed to levels approximately half of that observed during reinforced trials. A single treatment trial was then conducted in which some animals found water in the goal box and others continued to find an empty water bottle. Those subjects that were reinforced on treatment day subsequently demonstrated a reinstatement of their operant running response on the very next trial (i.e., 24 hr later). However, pretreatment with 1.0 mg/kg (but not 0.5 mg/kg) of the dopamine antagonist drug, pimozide, attenuated this response-reinstating effect of water-reinforcement. This action of pimozide was not likely a consequence of some residual sedative or motor incapacitation since a) the test day was conducted 24 hr after the treatment day by which time the pharmacological actions of the drug had greatly subsided; b) a Motor Control group administered pimozide after the reinforced trial exhibited normal response-reinstatement 24 hr later on Test Day; and c) on treatment day, pimozide did not reliably attenuate running times, latency to initiate drinking, nor the rate of licking behavior. Together, these data suggest that dopamine receptor antagonism can produce an attenuation in the reinforcing efficacy of water.

Animals↗
PubMed1976

Inhibition of mid-cycle gonadotrophin release in healthy women by pimozide and fusaric acid.

The effects of pimozide, a drug blocking dopamine receptors, and fusaric acid, an inhibitor of dopamine beta-hydroxylase, on mid-cycle release of FSH and LH were studied in 8 healthy women 20-25 years of age. None had used contraceptive drugs for the preceding 10 months. From the menstrual history and serum LH determinations during the normal cycle, mid-cycle gonadotrophin bursts were predicted for the following three cycles. Two days before and after the expected gonadotrophin surge were regarded as sufficient for the drug tests. Pimozide (initially 2 mg, then 1 mg/day) and fusaric acid (600 mg/day) were administered in a randomized cross-over study. The mid-cycle LH values were reduced from the control level of 56 +/- 10 mIU/ml (mean +/- SE) to 22 +/- 4 mIU/ml by pimozide (P less than 0.001) and to 17 +/- 5 mIU/ml by fusaric acid (P less than 0.001). The serum FSH level was 9 +/- 2 mIU/ml on the day of the LH surge and did not change significantly during treatment with either drug. The LH and FSH responses to synthetic LRF (100 mug iv) were not changed by pimozide or fusaric acid. The rise of basal temperature associated with ovulation was not affected by the drugs. These results suggest that suprapituitary noradrenergic and dopaminergic neurotransmitters are involved in the regulation of mid-cycle gonadotrophin secretion in women.

Adult↗
PubMed1992

Tamoxifen-resistant human breast cancer cell growth: inhibition by thioridazine, pimozide and the calmodulin antagonist, W-13.

Estrogen receptor (ER)-negative human breast cancer cell lines (MDA-MB-231 and MDA-MB-435) and ER-positive derivatives of the MCF-7 cell line selected for growth in the presence of antiestrogens (LY2 and RR) were used as in vitro models of tamoxifen-resistant human breast cancer in this study. The sensitivity of the tamoxifen-sensitive (MCF-7) and tamoxifen-resistant human breast cancer cell growth to two noncytotoxic neuroleptic drugs, pimozide and thioridazine, and the anticalmodulin agent, W-13, were compared. Inhibition of cell growth was measured as a decrease in cell number following a 72-h incubation with drug. Growth of the ER-negative cell lines MDA-MB-231 and MDA-MB-435 was inhibited by all three drugs. The average Ki values in these two lines were 6.3 and 3.8 microM for pimozide and 4.1 and 15 microM for thioridazine, respectively. Both ER-negative cell lines were more sensitive than MCF-7 cells to growth inhibition by W-13. MCF-7 cells selected for antiestrogen resistance were sensitive to growth inhibition by W-13 and thioridazine (LY2, average Ki = 10.4 microM; RR, average Ki = 5.2 microM). LY2 and RR cells were resistant to pimozide except when treated with estradiol (Ki = 4.6 and 7.9 microM, respectively). Pimozide, thioridazine and W-13 all exerted different effects on the distribution of human breast cancer cells within the cell cycle, suggesting that each drug may utilize a distinct pathway for inhibition of cell growth. We conclude that all three drugs are potential noncytotoxic alternatives to tamoxifen for the treatment of tamoxifen-resistant human breast cancer.

Breast Neoplasms↗
PubMed1991

[Three cases of hyponatremia during administration of pimozide].

Three patients with hyponatremia were found at an residential home of mental developmental delay. Because pimozide had been administered to all of them, it was suggested that pimozide might have induced compulsive water drinking resulting in hyponatremia. To my knowledge, there has been no previous report that pimozide may induce hyponatremia. As children with mental developmental delay and/or autism frequently develop epilepsy, hyponatremia should be included in the differential diagnosis of convulsive seizures. Particularly when antipsychotic drugs such as pimozide have been given, we should pay attention to polydipsia, polyuria and/or general malaise and prevent hyponatremia.

Adolescent↗
PubMed1990

Regulation of prolactin gene transcription in vivo: interactions between estrogen, pimozide, and alpha-ergocryptine.

A single injection of pimozide, a dopamine antagonist, rapidly stimulated prolactin (PRL) gene transcription in male rats, whereas an injection of alpha-ergocryptine, a dopamine agonist, rapidly inhibited PRL gene transcription. Pretreatment with cycloheximide blocked the induction of PRL gene transcription by pimozide but had no effect on the inhibition of transcription by ergocryptine. The interactions between ergocryptine and 16 alpha-estradiol, an estrogen that stimulates PRL gene transcription through two independent mechanisms, were also examined. Pretreatment with ergocryptine had no effect on the ability of 16 alpha-estradiol to stimulate PRL gene transcription through a mechanism that is most probably mediated directly by the anterior pituitary estrogen receptor. However, ergocryptine pretreatment did block the ability of 16 alpha-estradiol to stimulate transcription through a second, indirect, mechanism. This ergot alkaloid also blocked the ability of pimozide to stimulate PRL gene transcription. Pretreatment with 16 alpha-estradiol had no effect on the ability of ergocryptine to inhibit PRL gene transcription, indicating that this estrogen did not grossly alter the responsiveness of the anterior pituitary to the dopamine agonist. The similarities between the effects of 16 alpha-estradiol, via the indirect mechanism, and pimozide on PRL gene transcription suggest that estrogen may stimulate PRL gene transcription in vivo in part by reducing the release of dopamine from hypothalamic neurons.

Animals↗