Disease relevance of pimozide

• Treatment of metastatic malignant melanoma with pimozide [1].
• Here we present data that TI cells contain functional epithelial Na(+) channels (ENaC), pimozide-sensitive cation channels, K(+) channels, and the cystic fibrosis transmembrane regulator [2].
• The effects of pimozide on breast cancer cell growth were not limited to the MCF-7 cell line [3].
• Chlorpromazine, melittin, or pimozide also increased the toxicity of bleomycin to human granulocyte/macrophage and erythroid stem cell colonies [4].
• A 1-h exposure to nontoxic concentrations of the calmodulin antagonists melittin (0.5 microM), pimozide (5 microM), and chlorpromazine (20 microM) increased the lethality of bleomycin to human ovarian carcinoma cells (SK-OV) [4].

Psychiatry related information on pimozide

• Pimozide in treatment of anorexia nervosa [5].
• Controlled study of haloperidol, pimozide and placebo for the treatment of Gilles de la Tourette's syndrome [6].
• One week after discontinuation of pimozide treatment, the d-amphetamine-induced change as indicated by the Brief Psychiatric Rating Scale (BPRS) paranoid disturbance cluster score, was not significantly different from the response to a similar infusion during the drug-free state [7].
• With one exception (pimozide), all the drugs that suppressed cataplexy are known to be potent suppressors of REM sleep [8].
• CONCLUSIONS: Pimozide augmentation of fluoxetine treatment for body dysmorphic disorder was not more effective than placebo, even in more delusional patients [9].

High impact information on pimozide

• TII cells contain ENaC and cystic fibrosis transmembrane regulator, but few pimozide-sensitive cation channels [2].
• The germ cell T current is inhibited by antagonists of T-type channels (pimozide and amiloride) as well as by antagonists whose major site of action is the somatic cell L-type Ca2+ channel (1,4-dihydropyridines, arylalkylamines, benzothiazapines), as has also been reported for certain somatic cell T currents [10].
• In the present work, pimozide, thioridazine, W-13, and W-12 were shown to inhibit MCF-7 human breast cancer cell growth [3].
• Inhibition of human breast cancer cell proliferation in tissue culture by the neuroleptic agents pimozide and thioridazine [3].
• Pimozide also blocked cell growth and [3H]thymidine incorporation into the ER-positive T47D and ZR75-1B human breast cancer cell lines and the ER-negative human breast cancer cell line, MDA-MB-231 [3].

Chemical compound and disease context of pimozide

• We conclude that pimozide and thioridazine may be useful in the control of estradiol- and polypeptide hormone-induced growth of ER-positive and ER-negative human breast tumors [3].
• The growth of Y79 and WERI-Rb1 retinoblastoma cells, as well as MCF7 breast cancer epithelial cells, all of which express T-channel current and mRNA for T-channel subunits, is inhibited by pimozide and mibefradil with IC(50) values between 0.6 and 1.5 microM [11].
• Inspired by a previous study using pimozide, a double-blind placebo-controlled cross-over study with sulpiride was carried out in 18 female anorexia nervosa inpatients [12].
• The authors report in detail the case of a 27-year-old man who experienced sudden cardiac death 2 days after coprescription of the neuroleptic pimozide and the macrolide antibiotic clarithromycin after the documentation of a prolonged QT interval [13].
• Risperidone versus pimozide in Tourette's disorder: a comparative double-blind parallel-group study [14].

Biological context of pimozide

• Inhibition of MCF-7 cell growth by the selective calmodulin antagonists W-13 and W-12 is consistent with a role for calmodulin antagonism in the broad growth-inhibitory properties of pimozide [3].
• There was no significant effect of CYP2D6 or gender on the pharmacokinetics or pharmacodynamics of pimozide [15].
• The administration of phenoxybenzamine and pimozide per se did not significantly disturb cerebral blood flow or oxygen consumption [16].
• The seasonal variation in the ability of pimozide and phenoxybenzamine to increase LH secretion in ovary-intact ewes supports the hypothesis that inhibitory neural mechanisms suppressing GnRH are activated during anestrus and suggests that dopaminergic and/or alpha-adrenergic neurons are involved [17].
• Three thousand days of pregnancy. A case of monosymptomatic delusional pseudocyesis responding to pimozide [18].

Anatomical context of pimozide

• Reward-blocking doses of the neuroleptic pimozide activated the caudate and the lateral habenula but did not alter any of the unilateral effects of stimulation [19].
• Forebrain origins and terminations of the medial forebrain bundle metabolically activated by rewarding stimulation or by reward-blocking doses of pimozide [19].
• Pimozide inhibited LMC by 50% at 15 microM but caused a substantial decrease in lymphocyte ATP content and viability at this concentration [20].
• In whole-cell patch-clamp experiments, pimozide blocked Ca2+ current through L type channels of rat ventricular myocytes, in a voltage-dependent manner [21].
• Endocrine effects of pimozide, a specific dopaminergic blocker [22].

Associations of pimozide with other chemical compounds

• Among calmodulin antagonists tested, only trifluoroperazine inhibited Ca2+-stimulated secretion, whereas pimozide and calmidazolium did not [23].
• Drug therapy with benzhexol, tetrabenazine and pimozide or haloperidol may be beneficial in some cases [24].
• The authors present a case study that explores the relationship of dopamine function and manic illness through the use of two drugs with relatively specific effects in stimulating and blocking dopamine receptors--piribedil (ET--495) and pimozide, respectively [25].
• Twenty-six GTS patients (10.5 +/- 2.6 years), experienced clinical response rates of 69% on 3.4 +/- 1.6 mg pimozide and 65% on 3.5 +/- 2.2 mg/day haloperidol [26].
• Effect of gamma-aminobutyric acid on growth hormone and prolactin secretion in man: influence of pimozide and domperidone [27].

Gene context of pimozide

• Our results suggest that pimozide metabolism is catalyzed mainly by CYP3A, but CYP1A2 also contributes [28].
• Pimozide itself was a potent inhibitor of CYP2D6 in HLMs when preincubated for 15 min (Ki = 0.75 +/- 0.98 microM) and a moderate inhibitor of CYP3A (Ki = 76.7 +/- 34.5 microM), with no significant effect on other isoforms tested [28].
• Clarithromycin inhibited CYP3A-mediated pimozide metabolism and the resulting elevation in plasma concentrations may increase the risk of pimozide cardiotoxicity [15].
• Pimozide was without effect on SRIF release and did not alter the stimulatory effect of hGRF-40 [29].
• Tail-pinch- or CRF-induced food intake was blocked by naloxone, pimozide, and spiperone [30].

Analytical, diagnostic and therapeutic context of pimozide

• METHOD: A double-blind, 24-week, placebo-controlled double crossover study of equivalent dose formulations of haloperidol and pimozide was conducted with 22 subjects, aged 7-16 years, with Tourette's disorder who were randomly assigned to first one active drug treatment and then the other [31].
• The ECG QTc interval was significantly prolonged by pimozide but not haloperidol or placebo in a randomized clinical trial with 40 patients with Tourette's disorder [32].
• Positron emission tomography (PET) and 11C-labeled pimozide were used to study the dopaminergic (DA) receptor sites in the human striatum by comparing the latter with the cerebellum, which lacks DA receptors [33].
• 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 [34].
• Elevated SPL induced by a low dose of the dopaminergic blocker pimozide was suppressed after treatment with THC [35].

References