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PubMed2004

Delayed dystonia following pimozide overdose in a child.

BACKGROUND: Pimozide overdose has rarely been reported in children. In adults, pimozide intoxication may cause seizures, extrapyramidal and anticholinergic effects, hypotension, QTc prolongation and torsades de pointes. We report dystonia, hypotension and drowsiness following pimozide ingestion in a child. CASE REPORT: An alert 18-month-old presented to hospital 40 minutes after ingesting up to 6 mg (0.5 mg/kg) of pimozide. Vital signs: BP 91/62 mmHg, HR 130/min, RR 26/min, temperature 97.2 degrees F (36.2 degrees C). She received gastric lavage and activated charcoal. One hour later, her QTc interval was 420 msec, HR 150. She remained asymptomatic until 12 hours post-ingestion, when she developed drooling, tongue thrusting and drowsiness. BP was 75/40, HR 150, QTc 440 msec. BP increased to 95/50 after a bolus of normal saline. Her dystonia subsided over the next 12 hours without treatment. Drowsiness and tachycardia persisted until 40 hours post-ingestion. QTc interval at this time was 370 msec. Patient recovered without sequelae. CONCLUSION: Pimozide overdose in children may be associated with delayed onset of symptoms, including dystonia.

Adolescent↗
PubMed1986

Inhibition of gonadotropin secretion induced by cholecystokinin implants in the medial preoptic area by the dopamine receptor blocker, pimozide, in the rat.

We have shown that the implantation of cholecystokinin octapeptide sulfated form (CCK-8-S) or dopamine (DA) in the medial preoptic area (MPO) in ovariectomized estrogen-primed rats induced an enhancement of the afternoon rise in LH secretion. The present study was done to examine the possible functional interaction of both substances in the brain. Two groups of ovariectomized estradiol (5 micrograms, s.c.)-primed rats were administered intraperitoneally either pimozide (1 mg/kg BW; pimozide-treated group) or 0.1 M tartaric acid as the control solution (pimozide-untreated group). CCK-8-S or DA was implanted in the MPO through chronically implanted guide cannulae and the effects on serum LH and FSH concentrations were compared between both groups. An empty cannula was used as the control. Implantation of either CCK-8-S or DA in the pimozide-untreated group induced marked enhancements of afternoon rises in LH and FSH levels, which normally occurred, but with a lesser magnitude in the animals with the empty cannula. In the pimozide-treated group, however, neither CCK-8-S nor DA induced changes in the LH and FSH levels. It was evident that both effects of CCK-8-S and DA on LH and FSH secretion were blocked by pretreatment with the DA receptor blocker. These data indicate that DA receptors are required to be intact when CCK-8-S implants manifest their action in stimulating gonadotropin secretion.

Animals↗
PubMed2005

Placebo-controlled study of pimozide augmentation of fluoxetine in body dysmorphic disorder.

OBJECTIVE: Although body dysmorphic disorder often responds to serotonin reuptake inhibitors (SRIs), most patients do not respond or respond only partially. However, placebo-controlled studies of augmentation of SRIs have not been done. Furthermore, although 40%-50% of patients are delusional, studies of antipsychotic medications have not been done. METHOD: Twenty-eight patients with body dysmorphic disorder or its delusional variant participated in an 8-week, placebo-controlled, double-blind, parallel-group study of pimozide augmentation of fluoxetine. RESULTS: Pimozide was not more effective than placebo: two (18.2%) of 11 subjects responded to pimozide and three (17.6%) of 17 subjects responded to placebo. There was no significant effect of baseline delusionality on endpoint severity of body dysmorphic disorder. Delusionality did not decrease significantly more with pimozide than placebo. CONCLUSIONS: Pimozide augmentation of fluoxetine treatment for body dysmorphic disorder was not more effective than placebo, even in more delusional patients. Further studies of augmentation for SRIs are needed.

Adult↗
PubMed1982

Once weekly pimozide versus fluphenazine decanoate as maintenance therapy in chronic schizophrenia.

In a double blind trial, 28 male chronic schizophrenic in-patients received either pimozide, given once weekly, or fluphenazine decanoate, given mostly once fortnightly. There was no difference in relapse rates over nine months. However, three-quarters of the patients on pimozide who completed the trial developed at least mild tardive dyskinesia. All patients on pimozide lost weight, the average loss being 5.4 kg (12 lbs). Plasma pimozide levels suggested satisfactory drug compliance. Plasma prolactin levels confirmed that in the pimozide group there was fluctuating dopamine receptor antagonism, while in the fluphenazine group average plasma prolactin levels throughout most of the interval between injections were at the upper limit of normal.

Adult↗
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↗
PubMed2004

Pimozide in dermatologic practice: a comprehensive review.

Pimozide is an antipsychotic drug of the diphenylbutylpiperidine class. In the US, it is FDA-approved only as a backup treatment for Gilles de la Tourette syndrome, although it has been used in other countries for many years as a treatment for schizophrenia. In the past 20 years, pimozide has been found to be especially efficacious in the treatment of monosymptomatic hypochondriacal psychoses and is used by psychiatrists and dermatologists for this off-label purpose. In particular, pimozide is considered the treatment of choice for delusions of parasitosis. In addition, pimozide has been found to be efficacious in the treatment of body dysmorphic disorder, metastatic melanoma, trichotillomania, and trigeminal and postherpetic neuralgia. This review aims to familiarize physicians, especially dermatologists, on the uses of pimozide in dermatologic practice. A review of the literature was performed and the relevant information synthesized to give a complete overview of the drug and its therapeutic uses in dermatology.

Antipsychotic Agents↗
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↗
PubMed1982

Long-term pimozide pretreatment differentially affects behavioral responses to dextroamphetamine in schizophrenia. Further exploration of the dopamine hypothesis of schizophrenia.

In ten of 30 schizophrenic patients treated with pimozide for five weeks, 20 mg of dextroamphetamine sulfate induced an increase in psychosis. The number of patients becoming more psychotic with the dextroamphetamine challenge was not significantly different from the number who worsened after dextroamphetamine challenge when pretreated with placebo. Half of the patients who showed a psychotic response to dextroamphetamine during placebo pretreatment responded to dextroamphetamine with an increase in psychosis after pimozide treatment. Dextroamphetamine induced a worsening in patients who had improved with pimozide. The stability of the preinfusion condition is more important to the type of response to dextroamphetamine than long-term pretreatment with a dopamine receptor blocker. The activation-euphoria response to dextroamphetamine was unaffected by pimozide pretreatment, which suggests that the changes in psychosis and activation may be regulated by different mechanisms. These findings question the postulated relationship between the antipsychotic drug response and dopamine receptor blockade.

Adolescent↗
PubMed1988

Tests of functional equivalence between pimozide pretreatment, extinction and free feeding.

Both pimozide pretreatment and free feeding caused within-session and between-session decrements in variable interval operant performance; response decrements generated under pimozide were maintained on transfer to free feeding, and vice versa. On subsequently testing under extinction conditions (after food deprivation and drug free) large initial increases in responding were seen in all groups, and subsequent response decrements in extinction were steeper than in either pimozide or free feeding conditions. The effects of pimozide pretreatment do not resemble those of extinction, but may in some circumstances be functionally equivalent to a decrease in drive level.

Animals↗
PubMed1981

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

The effects of pimozide, a dopamine receptor-blocking agent, were studied in the pars intermedia of the rat. The animals received 100 microgram/100 g pimozide daily for 2, 5, 10, 15 and 20 days. Pimozide induces ultrastructural changes after 5 days of treatment. About 50% of the MSH-cells display characteristics of stimulation. Their cytoplasm is partially or totally depleted of secretory granules. The rough endoplasmic reticulum displays a network of interconnecting cisternae and ribbon-like structures. The well-developed Golgi complexes exhibit numerous dilatations of their cisternae, which contain electron-dense material. The nerve endings are not altered. Twenty days after treatment, the above-described changes have not decreased in magnitude. The present findings suggest that pimozide stimulates the mechanism of synthesis and release in some MSH-cells, most probably the elements underlying an inhibitory dopaminergic control.

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↗
PubMed1981

Effects of pimozide on nordiscriminated and discriminated performance in the pigeon.

The effects of pimozide (0.06, 0.18, 0.30 mg/kg), a dopamine receptor blocker, on nondiscriminated and discriminated performance were assessed in pigeons using a Latin Square design. In Experiment 1 a dose-dependent decrease in responding was observed with a variable interval 3-min schedule of reinforcement. More detailed analyses showed that total response rate, running response rate, and post-reinforcement pause all showed the same dose-dependent relationship. In Experiment 2 a successive discrimination task was employed to determine if pimozide affects a previously learned association between environmental stimuli. Each pigeon was first trained on the discrimination and then injected with the same doses as in Experiment 1. Although pimozide reduced responding in a dose-related fashion, a corresponding decrease in accuracy of responding was not evident. It was concluded that pimozide has a general response debilitating effect and that dopaminergic neurons probably are not involved in subserving associative processes.

Animals↗
PubMed1984

The effect of pimozide on variable-interval performance: a test of the 'anhedonia' hypothesis of the mode of action of neuroleptics.

A quantitative behavioural test system based on Herrnstein's (1970) equation was used to test a prediction derived from the "anhedonia" hypothesis of neuroleptic action, that pimozide should increase the value of the behavioural parameter KH (the reinforcement frequency needed to maintain the half-maximal response rate in variable-interval schedules). On the basis of theoretical considerations, it was shown that the equation implies that a drug which exerts such an effect on KH must have a more profound suppressant effect on performance maintained by low reinforcement frequencies than on performance maintained by high reinforcement frequencies. Fifteen rats were trained under variable-interval 10-s and variable-interval 100-s schedules, and the effect of pimozide (0.125, 0.25, 0.33, and 0.5 mg/kg) was tested on performance maintained under both schedules in a dose-dependent manner, and there was no tendency for the drug to exert a greater effect on performance maintained under the lower reinforcement frequency. These results do not provide any evidence that the effect of pimozide on variable-interval performance is due to an "anti-hedonic effect"; rather, they are compatible with the hypothesis that pimozide impairs the capacity to respond.

Animals↗
PubMed1985

The effects of pimozide on the establishment of conditioned reinforcement as a function of the amount of conditioning.

In an attempt to understand some inconsistent findings, the present experiment investigated the effects of pimozide, a dopamine (DA) receptor blocker, on the establishment of conditioned reinforcement as a function of the amount of conditioning. In Experiment 1, rats received three phases of training in a two-lever box. The pre-exposure phase measured the operant rates of pressing the levers; one produced a 3-s tone and the other turned the lights off for 3 s. In the conditioning phase, with the levers absent, the light-off stimulus was paired with food for two or four sessions. The test phase again measured the rate of pressing the levers. Conditioned reinforcement was shown by a relative increase in responding on the light lever during the test. Of the groups receiving four conditioning sessions, pimozide (0.5, 1.0, 2.0 and 4.0 mg/kg) produced a dose-dependent attenuation of conditioned reinforcement, those rats treated with 4.0 mg/kg failing to demonstrate a significant effect. When 2 conditioning days were employed, pimozide treatment also produced a dose-dependent attenuation; however, in these less conditioned animals 2.0 mg/kg blocked the effect. The possibility that pimozide produced a conditioned taste aversion to the food was ruled out in Experiment 2. These data suggest that DA transmission may be necessary for the establishment of conditioned reinforcement and that the effects of receptor blockade may be related to the amount of conditioning.

Animals↗
PubMed1983

The effects of dose and duration of chronic pimozide administration on dopamine receptor supersensitivity.

The neuroleptic drug pimozide was administered chronically to rats at different doses (0.75, 1.5 or 3.0 mg/kg, twice daily for 10 days) or for different durations (1.5 mg/kg twice daily for 5, 10, 20 or 40 days). At various intervals (4-40 days) after withdrawal dopamine (DA) receptor density in the striatum was assessed directly using specific [3H]-spiroperidol binding and indirectly by means of apomorphine-induced stereotypy and amphetamine-induced locomotor activity. The increase in the density of DA receptors was shown to be dependent upon the dose but not upon the duration of chronic pimozide. In contrast, the enhanced apomorphine-induced stereotypy was influenced by the duration but not by the dose of chronic pimozide. The potentiation of d-amphetamine-induced locomotor activity was found to vary as a function of both dose and duration of chronic pimozide administration. The results indicate that the augmentation of these apomorphine- and amphetamine-induced behaviors cannot be attributed solely to striatal DA receptor supersensitivity and that other, presently unspecified factors must contribute. It is also argued that in the absence of pharmacologically-induced DA receptor stimulation, the functional consequences of neuroleptic-induced increases in the density of striatal DA receptors are not apparent and remain unknown. In addition, these findings support the view that neuroleptic-induced proliferation of DA receptors cannot be the sole mechanism underlying tardive dyskinesia in man.

Animals↗
PubMed1990

Pimozide does not impair sweetness discrimination.

In an initial experiment pimozide decreased preference for a weak sucrose solution but increased preference for a strong solution on the descending limb of the concentration-intake function. As these effects resemble those of dilution, we therefore investigated whether pimozide decreases the perceived intensity of sweet stimuli. Rats were trained to perform a conditional discrimination in a T-maze. A correct response was rewarded by access to a 10% sucrose solution; an incorrect response was punished by confinement in the non-rewarded arm. In the first part of this experiment the discriminative stimulus, located at the choice point of the T-maze, was either water or sucrose, initially a 10% solution, but reduced gradually to 0.0003%. In the second part of the experiment, the discriminative stimulus was either 1% sucrose or a weaker solution, which was initially 0.0001% then raised gradually to 0.5%. Performance fell below 75% accuracy at 0 versus 0.0012% and at 1% versus 0.1%. Pimozide (0.5 mg/kg) administered at these (and other) levels of difficulty decreased running speed but had no effect on discrimination accuracy. As pimozide did not affect either the threshold for sweetness perception or the discrimination of a just noticeable difference, the decreased responsiveness of neuroleptic-treated rats to sweet rewards cannot be explained by a change in the perception of sweetness.

Animals↗
PubMed2000

Olanzapine in severe Gilles de la Tourette syndrome: a 52-week double-blind cross-over study vs. low-dose pimozide.

We selected four patients with severe Gilles de la Tourette syndrome, high frequency of tics (two to ten per minute), vocalizations, and lack of comorbidity. These patients (aged 19-40 years) underwent a 52-week double-blind cross-over study with olanzapine (5 and 10 mg daily) vs. low-dose pimozide (2 and 4 mg daily). The reduction in rating scale scores for the syndrome was highly significant with 10 mg olanzapine vs. basal and vs. 2 mg pimozide, and was significant for 5 mg olanzapine vs. 4 mg pimozide. Only moderate sedation was reported by one patient during olanzapine treatment while three complained of minor motor side effects and sedation during pimozide treatment. At the end of the study all patients opted for olanzapine treatment.

Adult↗