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PubMed1979

Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients.

The peripheral interactions of amphetamine with antipsychotic agents may elucidate some central mechanisms by which these drugs affect the behavioral responses to amphetamine. The authors studied the effects of intravenous amphetamine on plasma levels of norepinephrine (NE), dopamine-beta-hydroxylase (DBH), pulse rate, and blood pressure in schizophrenic patients. Amphetamine increased plasma NE, pulse rate, and blood pressure without significantly changing plasma DBH. DBH activity was similar in drug-free schizophrenic and normal subjects. Neither pimozide nor lithium altered these amphetamine effects nor changed any of the cardiovascular parameters measured in the drug-free subjects. Pimozide and lithium alter behavior and the behavioral effects of amphetamine, but neurotransmitters other than NE may be involved.

Adolescent↗
PubMed1996

Effect of pimozide on self-stimulation threshold under a continuous and fixed-interval schedule of reinforcement.

Rats implanted with a monopolar electrode in the medial mesencephalon and trained to press a lever to self-administer trains of stimulating pulses were tested under a continuous (CRF) and a fixed interval (FI-1s) schedule of reinforcement before and after systemic pimozide injection (0.35 mg/kg). As previously shown, this dose of pimozide caused reductions in maximal response rates and in the rewarding effectiveness of the stimulation. The magnitude of the attenuation in rewarding effectiveness was significantly greater under CRF than under FI conditions, an effect that can be attributed to the decrease in the number of earned rewards concomitant to a decrease in response rates. The present results show that the tighter control over reward density provided by the use of a FI schedule of reinforcement reduces the probability of artifactually measuring increases in reward thresholds following treatments that suppress response rates.

Animals↗
PubMedDate not supplied

Methadone, pentobarbital, pimozide and ethanol-intake.

For 28 days, water-deprived rats were given a daily, 1-hr opportunity to take a sweetened ethanol solution (ES) or water. Across days under this regimen, rats gained weight normally and increased intake of ES until they were taking considerable amounts. Across the next 13 days of the regimen, selected groups were given, before the opportunity to drink, one of five doses of methadone (from 0.5 to 8.0 mg/kg), pentobarbital (from 5 to 30 mg/kg), or their vehicles. Large doses of both agents increased intakes, with methadone (1 and 2 mg/kg) increasing only ES-intake. Subsequently, while the daily regimen continued, rats were given pimozide (0.2, 0.4, or 0.6 mg/kg) at either 1 or 4 hr before the opportunity to drink. Pimozide did not reduce ES-intake. Next, they were given a dose of pentobarbital (5.0 mg/kg) with challenge doses of naloxone (0.3, 1.0, 3.0 mg/kg). Naloxone dose-relatedly antagonized pentobarbital's potential to increase intakes.

Alcohol Drinking↗
PubMed2002

The effects of long-term testosterone, gonadotropin-releasing hormone agonist and pimozide treatments on testicular development and luteinizing hormone levels in juvenile and early maturing striped bass, Morone saxatilis.

The present study was conducted to test the responsiveness of the juvenile male reproductive axis to hormonal stimulation and to compare it to that of early maturing males. Long-term treatments with various combinations of T, GnRHa and pimozide did not result in an increased incidence of early maturing males, but did stimulate spermatogenesis slightly in juvenile fish. In early maturing males, the treatments appeared to be inhibitory since they resulted in a reduction of the GSI and a lower incidence of spermiating males. In early maturing males, pituitary LH content was elevated by GnRHa treatments alone while in juvenile males a combination of T and GnRHa was needed to increase the levels of LH in the pituitary. Thus, T may play an important role during puberty by potentiating the effects of GnRH on LH synthesis. In both juvenile and early maturing males, plasma LH levels could be increased only by high doses of GnRHa (in combination with T). Therefore, LH synthesis and release probably require different levels of GnRH stimulation. A GnRH challenge (single injection of 50 microg GnRHa/kg) at the end of the experiment resulted in a dramatic elevation of plasma LH levels in almost all animals. This finding demonstrates that pituitaries from juvenile and early maturing males were responsive to GnRHa stimulation, even after long-term hormonal treatments. The addition of pimozide did not affect the T- and GnRHa-induced increase in pituitary LH content but inhibited the release of LH in response to a GnRHa challenge. In conclusion, high doses of GnRHa in combination with T can increase plasma LH levels in juvenile males but do not induce complete testicular maturation. Factors other than T, GnRHa or LH are probably involved in the induction and completion of spermatogenesis.

Animals↗
PubMed1984

Some effects of pimozide on nondeprived rats licking sucrose solutions in an anhedonia paradigm.

The present work examines the generalizability of the anhedonia phenomenon (extinction-like responding with repeated neuroleptic treatment) by examining rats' licking behavior, a response heretofore untested, in the anhedonia paradigm. Nondeprived rats learned to lick a sucrose solution (32%) and were then tested for eight consecutive days in either a no-reward condition (N = 8) or two pimozide (PIM) with reward conditions (N = 8 at each of these two doses: 0.5 and 1.0 mg/kg). PIM treated animals did not exhibit rates or patterns of responding equivalent to animals in the extinction condition. Instead of an across session decline in rate, PIM treated animals showed a trend towards recovery on the rate measure. Within session patterns of responding of PIM treated animals more closely resembled animals in a normally rewarded condition responding at a generally lower rate, than animals in an extinction condition. The experimental procedure included the the use of home cage control animals, replication of the intermittent dosing procedure, and tests for transfer effects; all of these failed to produce patterns of responding typically obtained in the anhedonia paradigm when the response is lever pressing. Median lick duration and median interlick interval (ILI) were both lengthened with PIM treatment relative to injection control and extinction conditions, suggesting that pimozide treatment creates a motoric deficit. Taken together these results emphasize the importance of neuroleptics' motor vis a vis anhedonic effects.

Animals↗
PubMed1978

A comparative controlled trial of pimozide and fluphenazine decanoate in the continuation therapy of schizophrenia.

Evidence from a controlled, comparative trial indicates that oral pimozide is clinically at least as effective as depot injections of fluphenazine decanoate in the continuation therapy of a group of schizophrenic patients discharged from hospital. The administration of pimozide was associated with fewer unwanted effects. The implications of the findings are discussed.

Adult↗
PubMed1978

The social outcome of patients in a trial of long-term continuation therapy in schizophrenia: pimozide vs. fluphenazine.

A blind social assessment at home carried out twice during a year's follow-up of 41 patients on continuation therapy, 21 randomly allocated to pimozide tablets and 20 to fluphenazine decanoate injections. Patients on pimozide were significantly more favourably rated on aspects of sociability, use of leisure, warmth of personal relationships, household tasks and child-rearing. The mode of production of this result is discussed.

Adolescent↗
PubMed1975

Activity in chronic schizophrenic patients: comparison of pimozide with fluphenazine in a double blind trial.

A double-blind crossover trial was carried out comparing pimozide with fluphenazine. The effects of the drugs on the activity of 20 chronic inert male schizophrenic patients were measured using nursing observations, psychiatric rating, and an operant conditioning method. When activity was assessed in these different ways, no significant difference was found between the two drugs on any of the measures. It is concluded that pimozide does not effectively increase the activity in such patients. It is considered that the free operant conditioning method used was shown to be a useful measure for comparing therapy in chronic schizophrenic patients.

Administration, Oral↗
PubMed1987

Dopamine and preparatory behavior: I. Effects of pimozide.

The involvement of dopaminergic systems in appetitive and ingestive feeding behaviors was investigated in two experiments. Conditioned preparatory responses to a conditional stimulus (CS+) signaling delivery of a meal were attenuated in rats by doses of 0.4 and 0.6 mg/kg of the dopamine receptor antagonist pimozide. In contrast, animals responded in a normal fashion following the delivery of food. Similarly, in a separate study, the 20-min free-feeding intake of liquid diet by rats that had been deprived of food for 23 hr was unaffected by doses of pimozide as high as 0.6 mg/kg. These findings are consistent with the involvement of dopamine in the production of preparatory behaviors elicited by incentive stimuli.

Animals↗
PubMed1984

Effects of pimozide on escape and discrimination performance in a water-escape task.

The effects of pimozide (0.2 and 0.4 mg/kg) on discrimination learning were evaluated by a water-escape paradigm in which the degree of motor difficulty was manipulated by varying water temperature. Treatment with the drug marginally affected escape latencies in relatively warm water (25 degrees C) but markedly disrupted escape latencies when the task was more demanding (e.g., 15 degrees C and 20 degrees C water). The escape deficits, however, were not accompanied by disturbances in the acquisition of a position discrimination response or of a cue discrimination response when mice were required to make the highly prepared response of swimming to light or the contraprepared response of swimming to dark. These data were taken to suggest that in tasks involving aversive motivation pimozide influences performance through its effects on response maintenance but does not appear to affect either associative or motivational processes.

Animals↗
PubMed1998

Effects of long-term testosterone, gonadotropin-releasing hormone agonist, and pimozide treatments on gonadotropin II levels and ovarian development in juvenile female striped bass (Morone saxatilis).

The ability of the juvenile female reproductive axis to respond to hormonal stimulation was investigated in a Perciform fish, the striped bass (Morone saxatilis) using various combinations of testosterone (T), GnRH agonist (GnRHa), and pimozide. A long-term treatment with T alone, or T in combination with GnRHa, increased pituitary gonadotropin II (GtH II) levels 2- and 3-fold, respectively, suggesting that T and GnRHa each stimulate GtH II accumulation. Release of the accumulated GtH II could be induced only by high doses of GnRHa in combination with T, indicating that GtH II synthesis and release require different levels of GnRH stimulation. The addition of the dopamine antagonist pimozide did not affect pituitary and plasma GtH II levels but, in response to an additional acute GnRHa challenge, inhibited the release of GtH II. Although ovarian development was slightly stimulated by a combined T and GnRHa treatment, vitellogenesis was generally not initiated. The present study demonstrated that the juvenile striped bass pituitary is responsive to hormonal stimulation, resulting in elevated levels of GtH II in the pituitary and plasma. However, increased plasma levels of GtH II did not result in precocious puberty, suggesting that additional factors are required for the initiation of ovarian development in this teleost.

Animals↗
PubMed1993

Acute dystonic reaction with low-dose pimozide.

It is essential to recognize individual susceptibility to neuroleptic-induced side effects for treatment guidelines. This paper reports on a 6.9-year-old autistic male who developed repeated episodes of acute dystonic reactions associated with pimozide administration at the doses of 0.096 mg/kg/day and 0.032 mg/kg/day and 32 hours following pimozide withdrawal, as well as during subsequent thioridazine administration. It draws the clinician's attention to unusual susceptibility to extrapyramidal side effects and suggests that if a child shows this type of susceptibility to one neuroleptic, he/she may react similarly to other neuroleptics as well.

Autistic Disorder↗
PubMed1993

Improvement of trigeminal neurotrophic ulceration with pimozide in a cognitively impaired elderly woman--a case report.

Neurotrophic ulceration of the face is a rare but well recognized sequel to division of the trigeminal nerve. Trauma is an important contributory factor and thought to be due in part to paraesthesiae, which encourages picking and scratching, with resultant chronic and persistent ulceration. A case is described of an 82-year-old woman with severe trigeminal neurotrophic ulceration which improved substantially with pimozide, given for treatment of unrelated paranoid symptoms. The possible relevance of this to the established use of pimozide in delusional parasitosis is briefly discussed.

Aged↗
PubMed1993

Co-administration of the D2 antagonist pimozide inhibits up-regulation of dopamine release and uptake induced by repeated cocaine.

To investigate the hypothesis that the D2 dopamine (DA) receptor regulates DA uptake, as well as release, in the nucleus accumbens (N ACC), rats were pretreated for 10 days with either the selective D2 antagonist pimozide (1.0 mg/kg, i.p.) or vehicle, followed 3 h later by either cocaine (20 mg/kg, i.p.) or saline. On day 11, a microdialysis method was performed in which various DA concentrations (0, 10, and 20 nM DA) were perfused through the dialysis probe to characterize the diffusion of DA through tissue to and from the microdialysis probe (recovery). This diffusion of DA has been shown to be sensitive to changes in release and uptake. Pimozide pretreatment was shown to attenuate significantly a cocaine-induced increase in the in vivo recovery of DA (p < 0.01). The in vivo recovery for the vehicle/cocaine group was 47 +/- 4%, whereas the in vivo recovery for the pimozide/cocaine group was 31 +/- 3%. There was no difference between the pimozide/cocaine and control groups (pimozide/saline, 26 +/- 2%; vehicle/saline, 26 +/- 3%). In vitro probe calibrations indicated no significant difference in probe efficiencies between groups. These data suggest that the D2 receptor is capable of modulating uptake as well as release of DA in the N ACC of the rat.

Analysis of Variance↗
PubMed1982

Pimozide combined with behavior therapy in the short-term treatment of anorexia nervosa. A double-blind placebo-controlled cross-over study.

Eighteen female inpatients were included in a double-blind placebo-controlled cross-over study aimed at testing the hypothesis that dopamine blockade may enhance the effectiveness of behavior therapy in the short-term weight restoration of anorexia nervosa patients. The patients were given a uniform contingency management program and, after a baseline period, they alternatingly (3-week periods) received pimozide (4 to 6 mg) or a placebo. During the first two periods pimozide almost significantly enhanced the weight gain induced by the behavior therapy program and beneficially influenced the patients' attitude towards treatment.

Adolescent↗
PubMed1980

Effects of 6-hydroxydopamine and pimozide on temperature maintenance by the chicken.

Intraventricular implants of pimozide in adult white leghorn hens were used to block dopamine (DA) receptors, and 6-hydroxydopamine (6-OHDA) was injected intraventricularly to destroy the noradrenergic system locally. The hens were exposed to ambient temperatures of 5 and 35 degrees C, and their core temperature was measured. One hundred micrograms of 6-OHDA significantly reduced the norepinephrine (NE) but not the DA content of the hypothalamus and reduced the uptake of [3H]NE but not of [3H]DA by synaptosomes in vitro. Neither of the drug treatments nor their combination affected average core body temperature (Tb) at either 5 or 35 degrees C. Pimozide treatment caused a lower maximum Tb at 35 degrees C and a higher maximum Tb at 5 degrees C than the control treatment. No evidence was obtained that 6-OHDA treatment affected body temperature regulation. It is concluded that neither the DA nor the NE system is essential for normal temperature maintenance in the hen exposed to either 5 or 35 degrees C.

Animals↗
PubMed1987

Effect of pimozide on positive and negative symptoms in schizophrenic patients: are negative symptoms state dependent?

In a double-blind, placebo-controlled trial of treatment with the neuroleptic pimozide, negative symptoms improved in schizophrenic patients who showed an antipsychotic response. Furthermore, there was a significant positive correlation between changes in positive and negative symptoms for the group as a whole, including both pimozide responders and nonresponders. In our patient sample, neuroleptic treatment did not exert a differential effect on the positive and negative symptoms of schizophrenia. It is conceivable that negative symptoms are state dependent and may become neuroleptic nonresponsive over time just as positive symptoms do in some chronic patients.

Adolescent↗