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PubMed1982

Pimozide versus chlorpromazine in chronic schizophrenia: a 52 week double-blind study of maintenance therapy.

This study compared the effectiveness and safety of pimozide and chlorpromazine in the maintenance therapy of chronic schizophrenic outpatients. Forty-three patients were assigned in double-blind fashion to one of the drugs for the 52 week study. Both medication groups showed a general pattern of improvement over the course of the study, but there was no significant difference between the two groups. The results demonstrated the effectiveness and safety of pimozide in once daily administration. Previous research results showing the special utility of pimozide for the improvement of emotional withdrawal and social competence in schizophrenia were not replicated.

Adult↗
PubMedDate not supplied

[Use of pimozide (ORAP) in child psychiatry (author's transl)].

In a double blind cross-over study, pimozide was tested in 10 children with antisocial behavior. During two months, pimozide was administered orally between 1 and 2,6 mg per day. The use of a behavior scale permitted to conclude that pimozide improves social integration in the Socio-familial milieu.

Antisocial Personality Disorder↗
PubMedDate not supplied

A double blind study of pimozide versus chlordiazepoxide in anxiety neuroses.

Eighteen patients diagnosed as anxiety states were treated under double blind conditions for a four week trial period with pimozide and chlordiazepoxide after randomisation. No significant differences could be demonstrated between chlordiazepoxide and pimozide as far as therapeutic efficacy or toxicity were concerned. Pimozide administered in a single daily dose was as effective as chlordiazepoxide administered in divided daily doses for the relief of anxiety symptoms.

Adolescent↗
PubMed1975

[Experiences in the long term use of the 24 hour effective neuroleptic "pimozide" (Janssen)].

Pimozid (R 6238 Janssen, Beerse), a neuroleptic similar to the Butyrophenon type has a 24-hour period of effect due to the substance, and was used from 1969 onward on a total of 39 patients, predominantly from the range of schizophrenia types. The objective of thus clinical study was, above all, to plot the extent of its effects, define the optimal range of indications, to determine the most favourable dosage profile and to examine its tolerance in long-term use. Objectifying the medicinal effects, for example recording the psychopathological findings, proved successful with the aid of a syndrom catalogue following the AMP system, in comparison with preceeding and following treatments and considering the social-psychiatric aspects, so that concomitant- and side effects can be ascertained in the same way. The necessary maintenance dose of Pimozid, usually administered once a day, was set in relation to the daily dosage of Haloperidol, which had to be administered 2 to 3 times daily; the results, meanwhile, were compared with those already recorded on the literature. In agreement with this Pimozid proved to be a powerful and well tolerated neuroleptic, even in older patients, with a constant 24-hour effect which is suitable in doses from 1--10 mg/d particularly for long-term out-patient therapy, and above all for psychotics of the paranoid hallucinatory type.

Adolescent↗
PubMed1977

Effects of alpha-methyl-p-tyrosine, adrenolytic compounds, pimozide and other neuroleptics, on the narcotic cue.

Using a two-lever food-reinforced operant procedure, rats (n=11) were trained to discriminate the narcotic analgesic fentanyl (0.04 mg/kg, s.c.) from saline. In rats so trained, alpha methyl-p-tyrosine (150 mg/kg, i.p.) was found not to affect the discriminability of fentanyl. Pretreatment (s.c.) with either adrenolytic compounds (10 mg/kg aceperone, 40 mg/kg dibenamine, 10 mg/kg phenoxybenzamine, 20 mg/kg propranolol) or sedative neuroleptics (0.63 mg/kg azaperone, 1.25 mg/kg chlorpromazine, 10 mg/kg pipamperone) likewise failed to attenuate the narcotic cue. Pimozide (0.63 mg/kg) and, to some extent, spiperone (0.04 mg/kg) reduced the percentage of responding on the selected lever, and pimozide antagonized drug lever selection in some animals. The results suggest that specific neuroleptics (e.g. pimozide) may affect the subjective effects induced by narcotics in humans.

Animals↗
PubMed1997

Modified radioimmunoassay for pimozide.

Tritium labelled pimozide, the tracer in Michiels' RIA of pimozide, can be substituted for a derivative of pimozide with tritium labelled tag, prepared in a more convenient way than the original tracer. In the synthesis of the immunogen the conjugation rate is optimized to be 12 to 13.

Animals↗
PubMed1976

The ability of pimozide to prevent inhibition by dopamine analogs of cardioaccelerator nerves in cat hearts.

The dopamine receptor blocking agent, pimozide, antagonized inhibitory actions of apomorphine, N,N-dimethyldopamine and 5,6-dihydroxy-2-dimethyl-aminotetralin (M-7) on stimulation-induced positive chronotropic responses of cat hearts in both in vivo and in vitro experiments. Pimozide did not antagonize the inhibitory effect of clonidine in vitro experiments. Phentolamine, an alpha-adrenergic blocking agent, antagonized the inhibitory actions of dopamine analogs at 1.10 mug/ml concentration in in vitro experiments. Phentolamine, 0.3 mug/ml, only attenuated the response of N, N-dimethyldopamine but did not antagonize the effects of apomorphine and M-7. Lower concentration of phentolamine, 0.1 mug/ml, showed marked inhibition to the inhibitory effect of clonidine. Both phentolamine and pimozide potentiated stimulation-induced positive chronotropic responses of cat right atria. Possibility of the presence of dopaminergic inhibitory system near the alpha-adrenergic inhibitory system in cardioaccelerator nerve terminal is discussed.

Animals↗
PubMedDate not supplied

[Assessment of the efficacy of treatment with pimozide in patients with amyotrophic lateral sclerosis. Introductory notes].

The aim of the study was to assess the effect of pimozide voltage-dependent calcium channel blocker on the progression of ALS patients as compared to the potentially neuroprotective drugs, selegiline and vitamin E. There were 44 patients (17 females and 27 males, aged from 30 to 80 years, mean age: 56.2 years) diagnosed as either definite or possible ALS. The study design was open randomised. Patients were treated 3-12 months; the daily dose of pimozide was 1 mg. The disease progression index was calculated as a difference between scores of Norris scale before and after treatment. Statistical analysis showed a significant decrease of the index of progression of the disease in pimozide treated patients as compared to the others. This effect was neither related to the progression of the disease nor advance of the disease at the beginning of treatment.

Adult↗
PubMedDate not supplied

Dopamine and temperature regulation in the primate: effects of apomorphine and pimozide.

The purpose of this study was to determine the effects of a specific dopamine-receptor agonist (apomorphine) and antagonist (pimozide) on temperature regulation in the primate. Using 4 rhesus monkeys and 2 patas monkeys as subjects, increasing doses of apomorphine (0.05, 0.1, 0.2, 0.4, 0.6 mg/kg) injected subcutaneously produced a dose-dependent hypothermia associated with sharp elevations in tail-skin and ear pinna temperatures. Apomorphine also produced dose-related behavioral responses including salivation, hypermotility, hypersensitivity, pupil dilation and erection, suggesting a central site of action. Pre-treatment with pimozide (0.5 mg/kg, SC) blocked the apomorphine-induced hypothermia, but the subcutaneous injection of pimozide alone had no effect on body temperatures. In the patas monkey, the decline in colonic temperature following the injection of apomorphine (0.4 mg/kg) was not associated with a change in metabolic rate or heart rate. In 2 animals, mean colonic temperature fell 1.7, 0.67, and 0.3 degrees C following the injection of apomorphine ((0.4 mg/kg) in 15, 25, and 35 degrees C environments, respectively. These data suggest that the apomorphine-induced hypothermia was mediated by an increase in heat dissipation rather than a decline in heat production. The site of this drug remains to be elucidated.

Apomorphine↗
PubMed1994

Changes in plasma levels of 17 beta-estradiol after administration of an analogue of luteinizing hormone releasing hormone (LHRH-A) and pimozide in Diplectrum formosum (Teleostei: Serranidae).

Gonadotropin secretion in teleosts is known to be stimulated by gonadotropin hormone releasing hormone (GnRH) and inhibited by dopamine. This study has investigated the effects of administration of pimozide (PIM) alone or in combination with an analogue of GnRH on plasma 17 beta-estradiol (17 beta-E) levels and the gonadosomatic index. Adult Diplectrum formosum were treated with a gonadotropin-releasing hormone analogue [des-Gly10 D-Ala6 Pro9 N-ethylamide (LHRH-A); 50, 70, and 100 ng/g body wt] alone or in combination with pimozide (PIM), a dopamine antagonist (0.5, 1.0, and 5.0 micrograms/g body wt). LHRH-A alone caused a dose-dependent increase in plasma 17 beta-E levels. A single injection of PIM (0.5 or 5.0 micrograms/g) 12 hr previous to a single injection of 100 ng/g body wt of LHRH-A increased 17 beta-E concentrations compared with fish receiving PIM alone; however, 1 microgram/g PIM did not change 17 beta-E plasma levels. Simultaneous administration of PIM (0.5, 1.0, and 5.0 micrograms/g body wt) and 100 ng/g body wt of LHRH-A at an interval of 12 hr (30% of the total dose of both PIM and LHRH-A was administered in the first injection and 70% in the second injection) significantly increased plasma 17 beta-E concentrations. The magnitude of this increase was at least threefold higher than those of fish receiving a single injection of PIM, 12 hr before a single injection of LHRH-A. LHRH-A or PIM alone or combined was ineffective in causing ovulation.

Animals↗
PubMed1986

Chlorpromazine and pimozide alter reinforcement efficacy and motor performance.

This study evaluated the effects of chlorpromazine and pimozide on reinforced responding. In each session, rats were exposed to a series of five variable-interval reinforcement schedules. The response requirement was a lever press, the reward was a small portion of water, and the reinforcement rate varied from about 20 to 660 reinforcers per hour. Response rate was a negatively accelerated function of reinforcement rate, and the relationship between the two variables was described by the equation for a rectangular hyperbola (the matching law). One parameter of the hyperbola is equivalent to the asymptotic response rate and the other parameter is equivalent to the rate of reinforcement that maintains a one-half asymptotic response rate. Chlorpromazine (0.75-3.0 mg/kg) and pimozide (0.1-0.4 mg/kg) dose-dependently decreased response rates. At low doses, the response rate decreases were, for the most part, restricted to the low reinforcement rate schedules. In contrast, the highest dose tested decreased response rates at both low and high reinforcement rates. The patterns of response rate decreases resulted in dose-dependent changes in the parameters of the matching law equation. The shifts in the matching law parameters were discussed in terms of the motoric and motivational interpretations of neuroleptic-induced response rate changes.

Animals↗
PubMed1987

Expression of morphine-conditioned hyperactivity is attenuated by naloxone and pimozide.

The present experiments assessed whether morphine-conditioned hyperactivity could be attenuated by either the opiate antagonist naloxone or the dopamine antagonist pimozide. Both of these antagonists were shown to block the unconditioned hyperactivity induced by 2 mg/kg morphine (Experiment 1). Rats were then conditioned by pairing this dose of morphine repeatedly with a distinctive environment (Experiment 2). Following several drug-environment pairings, rats displayed a hyperactive conditioned response (CR) when exposed to the environment in the absence of the drug. CR expression was counteracted by 1 mg/kg naloxone and was attenuated by pimozide (0.25, 0.33, and 0.4 mg/kg) in a dose-related manner. These findings suggest that the unconditioned and conditioned hyperactive responses produced by morphine may involve similar neuropharmacologic substrates.

Animals↗
PubMed1987

Effects of extinction, pimozide, SCH 23390, and metoclopramide on food-rewarded operant responding of rats.

The similarity in the pattern of responding produced by extinction and dopamine (DA) receptor blockers has led to the suggestion that DA neurons may participate in the usual effects of reward on behaviour. The purpose of the present study was to evaluate the effect of receptor-subtype specific DA antagonists on food-rewarded operant responding. Rats were trained to lever press for food on a variable interval 30-s schedule. They then received one of the following treatments prior to testing on the next 5 days: saline, nonreinforcement, the DA receptor blocker pimozide (0.5 or 1.0 mg/kg), the D1 receptor blocker SCH 23390 (0.01, 0.05, 0.1 mg/kg), and the D2 receptor blocker metoclopramide (1.0, 5.0, 10.0 mg/kg). Nonreinforcement resulted in both intra- and intersession declines in responding. The drugs produced dose-dependent decreases in overall responding. Additionally, both doses of pimozide and the higher doses of SCH 23390 and metoclopramide altered intrasession patterns of responding when compared to saline, with their greatest effect being in the latter portion of the session. Intersession declines were seen with the highest doses of SCH 23390 and metoclopramide and control studies showed that these declines could not be attributed to a buildup of the drug with repeated dosing. It was concluded that both D1 and D2 receptors participate in the control of behaviour by reward.

Animals↗
PubMed1988

Scopolamine produces environment-specific conditioned activity that is not blocked by pimozide in rats.

A classical conditioning paradigm was employed to determine if the stimulant effects of the anticholinergic scopolamine could show conditioning. In experiment 1 rats had 12 60-min pairings of scopolamine (1.0 or 8.0 mg/kg, IP) with a distinctive environment that monitored horizontal and vertical activity. Experimental (paired) groups received the drug 30 min prior to each session, whereas control (unpaired) groups received saline. Following each session the Paired groups were injected with saline, and the Unpaired groups received the same doses of scopolamine. After every fourth pairing a test session assessed conditioning by comparing activity of paired und unpaired groups in response to saline. Scopolamine enhanced horizontal activity, although conditioning was seen only with 8.0 mg/kg. The low dose increased vertical activity, whereas an initial decrease was observed with 8.0 mg/kg. However, conditioned vertical activity was seen with both doses. Experiment 2 assessed the possible role of dopamine in conditioning with 8.0 mg/kg scopolamine. Rats treated as in experiment 1 were additionally given 0.4 mg/kg pimozide 4 h prior to each pairing session. Pimozide did not block scopolamine's stimulant effect. Conditioned horizontal and vertical activity were also observed, suggesting that this effect may be mediated by direct changes within cholinergic systems.

Animals↗
PubMed1978

Effects of pimozide and bromocriptine on anterior pituitary cell proliferation.

The effects of pimozide (a dopamine receptor blocker) and bromocriptine (a dopamine receptor agonist) on the mitotic incidence in the anterior pituitary in male rats was investigated. It was shown that pimozide enhanced anterior pituitary mitotic activity in male rats. Bromocriptine, in turn, suppressed anterior pituitary cell proliferation in estradiol-treated male rats. A dopaminergic control of anterior pituitary mitotic activity is suggested.

Animals↗
PubMed1991

Time-, schedule-, and reinforcer-dependent effects of pimozide and amphetamine.

Rats performed on two multiple random-interval schedules, in which sequences of ascending or descending reinforcement densities were balanced between the schedules and between the two halves of the session. Using a standard reinforcer (10% sucrose pellets), pimozide decreased response rates, while amphetamine increased responding. The effects of both drugs were schedule dependent: larger changes were evident in low response rate, reinforcement-lean components than in high response rate, reinforcement-rich components. Both effects were also time dependent, increasing over the course of the session; this casts serious doubt on the applicability of Herrnstein's matching law for studying agents acting on brain dopamine. Increasing the period of food deprivation increased response rates, while withdrawing food deprivation decreased responding. These effects were also schedule dependent, but were time dependent. Substituting 95% sucrose pellets for standard 10% sucrose pellets caused an immediate and sustained decrease in responding, and up to 10% of earned reinforcement was not consumed. Pimozide increased response rates within reinforcement-lean components and reinstated the complete consumption of earned reward typical of standard reinforcement. These apparently paradoxical effects may be consistent with a decrease in the rewarding properties of sucrose pellets. Despite low response rates, amphetamine did not affect responding maintained by 95% sucrose pellets but did further reduce the consumption of earned reward. These results call into question the generality of the rate-dependency principle in the action of psychomotor stimulants.

Amphetamine↗
PubMed1979

In vitro effect of dopamine and pimozide on human chorionic gonadotropin secretion.

In human placental explants cultured in vitro, dopamine inhibited human chorionic gonadotropin (hCG) secretion into the culture media. In the control flasks, the level of hCG secretion was 751 +/- 215 mIU/gm of tissue. When 1 mM of dopamine was added, hCG levels decreased to 321 +/- 57.6 mIU/gm of tissue (n = 6, P less than 0.1)--5 and 10 mM of dopamine significantly inhibited hCG secretion. In contrast, 1 mM of pimozide enhanced hCG secretion by 1.8-fold compared to control levels (1,707 +/- 343 versus 3,117 +/- 0.005). This in vitro effect on hCG is similar to the effect of dopamine and pimozide on hCS secretion by placental explants.

Chorionic Gonadotropin↗
PubMed1975

Cholinergic-dopaminergic interaction in the striatum: the effect of 6-hydroxydopamine or pimozide treatment on the increased striatal acetylcholine levels induced by apomorphine, piribedil and d-amphetamine.

Apomorphine (1 and 2 mg/kg), piribedil (15 and 60 mg/kg) and d-amphetamine (5 and 10 mg/kg) increased rat striatal acetylcholine levels without affecting choline. Pretreatment with pimozide (0.5 mg/kg) completely antagonized the effect of apomorphine and piribedil and by itself markedly decreased striatal acetylcholine levels. d-Amphetamine signigicantly antagonized the effect of pimozide. Nine days after pretreatment with 6-hydroxydopamine plus pargyline, striatal dopamine was decreased by 78% while acetylcholine and choline levels remained unaltered. Under these conditions, the effect of d-amphetamine was completely abolished while apomorphine and piribedil were just as active as in the vehicle-treated group. The results suggest that d-amphetamine acted indirectly to increase striatal acetylcholine levels probably through the release of dopamine and/or noradrenaline, while apomorphine and piribedil acted directly at dopamine receptor sites.

Acetylcholine↗