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Chemical Compound Review

Haldol     4-[4-(4-chlorophenyl)-4- hydroxy-1...

Synonyms: Brotopon, Eukystol, Fortunan, Halojust, Halosten, ...
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Disease relevance of haloperidol

  • In the past nine years, we have treated 11 patients who had an acute onset of hemiballismus believed to be the result of an acute vascular lesion with neuroleptic drugs (most frequently haloperidol) [1].
  • Pavlovian conditional tolerance to haloperidol catalepsy: evidence of dynamic adaptation in the dopaminergic system [2].
  • In two cebus (Cebus albifrons) monkeys given weekly oral doses of 0.25 milligram of haloperidol per kilogram, movement disorders appeared 1 to 8 hours after drug administration following the tenth weekly dose [3].
  • Haloperidol for organic brain disorders [4].
  • Despite the lack of concrete evidence, both the clinical and morphologic features, and the close temporal relationship between the medication and onset of illness in this patient led to the reasonable inference that haloperidol was responsible for the chronic cholestatic reaction on a hypersensitivity basis [5].

Psychiatry related information on haloperidol


High impact information on haloperidol


Chemical compound and disease context of haloperidol


Biological context of haloperidol

  • In contrast, evidence of increased dopamine-receptor sensitivity was observed in the pups if haloperidol was administered to their mothers postpartum during nursing rather than during pregnancy [21].
  • A second case of severe limb malformations was observed following maternal use of haloperidol early in the first trimester of pregnancy [22].
  • The sigma enigma: biochemical and functional correlates emerge for the haloperidol-sensitive sigma binding site [23].
  • Following chlorpromazine therapy, but not following haloperidol treatment, plasma NE level increased with patients supine and standing, pulse rate increased with patients standing, and systolic BP decreased with patients standing [24].
  • Subjects treated with clozapine experienced more excess salivation, dizziness, and sweating and less dry mouth and decreased appetite than those treated with haloperidol [25].

Anatomical context of haloperidol


Associations of haloperidol with other chemical compounds


Gene context of haloperidol

  • Intracerebroventricular injections of 300-3000 pmol of either NPY, PYY, NPY2-36, or the Y1 agonist Leu31,Pro34-NPY inhibited significant proportions (17-35%) of haloperidol-sensitive in vivo 3H-(+)SKF 10,047 hippocampal labeling [35].
  • Neither withdrawal of drug treatment in patients nor chronic administration of haloperidol to rats altered levels of BDNF [36].
  • Chronic treatment of animals with the antipsychotic drug haloperidol had no influence on EGF levels in the brain or serum [37].
  • Our results suggest that haloperidol can be used as a tool for investigating NMDA receptor subunit composition and can serve as a structural lead for designing novel subtype-selective NMDA receptor ligands [38].
  • Of a range of ligands studied, only haloperidol functioned as a neutral ligand in the presence of RGS1 [39].
  • The sustained levels of BDNF in rats with rhEPO prevented the haloperidol-induced increase in caspase-3 (p<0.05) and decrease in Bcl-xl (p<0.01) protein levels [40].

Analytical, diagnostic and therapeutic context of haloperidol

  • These behavioral alterations are similar to those observed in pharmacologically induced animal models of schizophrenia and can be ameliorated by treatment with haloperidol or clozapine, antipsychotic drugs that antagonize dopaminergic and serotonergic receptors [41].
  • Over a one-year period, patients assigned to clozapine had fewer mean days of hospitalization for psychiatric reasons than patients assigned to haloperidol (143.8 vs. 168.1 days, P=0.03) and used more outpatient services (133.6 vs. 97.9 units of service, P=0.03) [42].
  • Moreover, the effect of 5 mug per kg of dopamine was blocked by haloperidol but not by phentolamine, propranolol, bilateral cervical vagotomy, or tetrodotoxin [29].
  • A D2-receptor preparation partially purified by affinity chromatography on a haloperidol adsorbent, exhibited agonist-stimulated GTPase activity [43].
  • The relative efficacy of three oral regimens of haloperidol was compared in a ten-day, double-blind study of 63 acutely ill schizophrenic patients newly admitted to the hospital [44].


  1. Treatment and prognosis of hemiballismus. Klawans, H.L., Moses, H., Nausieda, P.A., Bergen, D., Weiner, W.J. N. Engl. J. Med. (1976) [Pubmed]
  2. Pavlovian conditional tolerance to haloperidol catalepsy: evidence of dynamic adaptation in the dopaminergic system. Poulos, C.X., Hinson, R. Science (1982) [Pubmed]
  3. Dyskinesias evoked in monkeys by weekly administration of haloperidol. Weiss, B., Santelli, S. Science (1978) [Pubmed]
  4. Haloperidol for organic brain disorders. Davis, J.A. JAMA (1979) [Pubmed]
  5. Haloperidol-induced chronic cholestatic liver disease. Dincsoy, H.P., Saelinger, D.A. Gastroenterology (1982) [Pubmed]
  6. A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia. Csernansky, J.G., Mahmoud, R., Brenner, R. N. Engl. J. Med. (2002) [Pubmed]
  7. Low-dose haloperidol for stereotypic self-injurious behavior in the mentally retarded. Mikkelsen, E.J. N. Engl. J. Med. (1986) [Pubmed]
  8. Transdermal nicotine patch and potentiation of haloperidol in Tourette's syndrome. Silver, A.A., Sanberg, P.R. Lancet (1993) [Pubmed]
  9. Akathisia with haloperidol and thiothixene. Van Putten, T., May, P.R., Marder, S.R. Arch. Gen. Psychiatry (1984) [Pubmed]
  10. Carbamazepine and haloperidol v placebo and haloperidol in excited psychoses. A controlled study. Klein, E., Bental, E., Lerer, B., Belmaker, R.H. Arch. Gen. Psychiatry (1984) [Pubmed]
  11. Haloperidol differentially modulates prepulse inhibition and p50 suppression in healthy humans stratified for low and high gating levels. Csomor, P.A., Stadler, R.R., Feldon, J., Yee, B.K., Geyer, M.A., Vollenweider, F.X. Neuropsychopharmacology (2008) [Pubmed]
  12. Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia. Emamian, E.S., Hall, D., Birnbaum, M.J., Karayiorgou, M., Gogos, J.A. Nat. Genet. (2004) [Pubmed]
  13. Neurotensin blocks certain amphetamine-induced behaviours. Ervin, G.N., Birkemo, L.S., Nemeroff, C.B., Prange, A.J. Nature (1981) [Pubmed]
  14. Perinatal dopamine-related drugs demasculinize rats. Hull, E.M., Nishita, J.K., Bitran, D., Dalterio, S. Science (1984) [Pubmed]
  15. Haloperidol-induced plasticity of axon terminals in rat substantia nigra. Benes, F.M., Paskevich, P.A., Domesick, V.B. Science (1983) [Pubmed]
  16. Dementia induced by methyldopa with haloperidol. Thornton, W.E. N. Engl. J. Med. (1976) [Pubmed]
  17. Comparison of pimozide with haloperidol in Gilles de la Tourette syndrome. Rose, M.S., Moldofsky, H. Lancet (1977) [Pubmed]
  18. Nicotine gum and haloperidol in Tourette's syndrome. Sanberg, P.R., Fogelson, H.M., Manderscheid, P.Z., Parker, K.W., Norman, A.B., McConville, B.J. Lancet (1988) [Pubmed]
  19. Behavioral efficacy of haloperidol and lithium carbonate. A comparison in hospitalized aggressive children with conduct disorder. Campbell, M., Small, A.M., Green, W.H., Jennings, S.J., Perry, R., Bennett, W.G., Anderson, L. Arch. Gen. Psychiatry (1984) [Pubmed]
  20. Clonidine and haloperidol in Gilles de la Tourette syndrome. Shapiro, A.K., Shapiro, E. Arch. Gen. Psychiatry (1981) [Pubmed]
  21. Enduring changes in dopamine receptor cells of pups from drug administration to pregnant and nursing rats. Rosengarten, H., Friedhoff, A.J. Science (1979) [Pubmed]
  22. Limb malformations following maternal use of haloperidol. McCullar, F.W., Heggeness, L. JAMA (1975) [Pubmed]
  23. The sigma enigma: biochemical and functional correlates emerge for the haloperidol-sensitive sigma binding site. Chavkin, C. Trends Pharmacol. Sci. (1990) [Pubmed]
  24. Plasma norepinephrine and dopamine-beta-hydroxylase activity in schizophrenia. Castellani, S., Ziegler, M.G., van Kammen, D.P., Alexander, P.E., Siris, S.G., Lake, C.R. Arch. Gen. Psychiatry (1982) [Pubmed]
  25. Clozapine and haloperidol in moderately refractory schizophrenia: a 6-month randomized and double-blind comparison. Kane, J.M., Marder, S.R., Schooler, N.R., Wirshing, W.C., Umbricht, D., Baker, R.W., Wirshing, D.A., Safferman, A., Ganguli, R., McMeniman, M., Borenstein, M. Arch. Gen. Psychiatry (2001) [Pubmed]
  26. Amphetamine, haloperidol, and experience interact to affect rate of recovery after motor cortex injury. Feeney, D.M., Gonzalez, A., Law, W.A. Science (1982) [Pubmed]
  27. The antiinflammatory effect of dopamine in alcoholic hemorrhagic pancreatitis in cats. Studies on the receptors and mechanisms of action. Karanjia, N.D., Widdison, A.L., Lutrin, F.J., Chang, Y.B., Reber, H.A. Gastroenterology (1991) [Pubmed]
  28. Central neurotensin inhibits gastric acid secretion: an adrenergic mechanism in rats. Zhang, L., Xing, L.P., Demers, L., Washington, J., Kauffman, G.L. Gastroenterology (1989) [Pubmed]
  29. Effect of dopamine on the esophageal smooth muscle in vivo. Rattan, S., Goyal, R.K. Gastroenterology (1976) [Pubmed]
  30. Adverse reactions in treatment with lithium carbonate and haloperidol. Baastrup, P.C., Hollnagel, P., Sorensen, R., Schou, M. JAMA (1976) [Pubmed]
  31. Haloperidol antagonism of cue-elicited cocaine craving. Berger, S.P., Hall, S., Mickalian, J.D., Reid, M.S., Crawford, C.A., Delucchi, K., Carr, K., Hall, S. Lancet (1996) [Pubmed]
  32. Peptide YY inhibition of prostaglandin-induced intestinal secretion is haloperidol-sensitive in humans. Rozé, C., Molis, C., Xiaomei, F.C., Ropert, A., Genève, J., Galmiche, J.P. Gastroenterology (1997) [Pubmed]
  33. Increased levels of transcription factors Elk-1, cyclic adenosine monophosphate response element-binding protein, and activating transcription factor 2 in the cerebellar vermis of schizophrenic patients. Kyosseva, S.V., Elbein, A.D., Hutton, T.L., Griffin, S.T., Mrak, R.E., Sturner, W.Q., Karson, C.N. Arch. Gen. Psychiatry (2000) [Pubmed]
  34. Plasma homovanillic acid as a predictor of response to neuroleptics. Davila, R., Manero, E., Zumarraga, M., Andia, I., Schweitzer, J.W., Friedhoff, A.J. Arch. Gen. Psychiatry (1988) [Pubmed]
  35. Evidence for in vivo interactions between neuropeptide Y-related peptides and sigma receptors in the mouse hippocampal formation. Bouchard, P., Dumont, Y., Fournier, A., St-Pierre, S., Quirion, R. J. Neurosci. (1993) [Pubmed]
  36. Abnormal expression of brain-derived neurotrophic factor and its receptor in the corticolimbic system of schizophrenic patients. Takahashi, M., Shirakawa, O., Toyooka, K., Kitamura, N., Hashimoto, T., Maeda, K., Koizumi, S., Wakabayashi, K., Takahashi, H., Someya, T., Nawa, H. Mol. Psychiatry (2000) [Pubmed]
  37. Abnormal expression of epidermal growth factor and its receptor in the forebrain and serum of schizophrenic patients. Futamura, T., Toyooka, K., Iritani, S., Niizato, K., Nakamura, R., Tsuchiya, K., Someya, T., Kakita, A., Takahashi, H., Nawa, H. Mol. Psychiatry (2002) [Pubmed]
  38. Subtype-selective inhibition of N-methyl-D-aspartate receptors by haloperidol. Ilyin, V.I., Whittemore, E.R., Guastella, J., Weber, E., Woodward, R.M. Mol. Pharmacol. (1996) [Pubmed]
  39. Enhanced detection of receptor constitutive activity in the presence of regulators of G protein signaling: applications to the detection and analysis of inverse agonists and low-efficacy partial agonists. Welsby, P.J., Kellett, E., Wilkinson, G., Milligan, G. Mol. Pharmacol. (2002) [Pubmed]
  40. Erythropoietin prevents haloperidol treatment-induced neuronal apoptosis through regulation of BDNF. Pillai, A., Dhandapani, K.M., Pillai, B.A., Terry, A.V., Mahadik, S.P. Neuropsychopharmacology (2008) [Pubmed]
  41. Mice with reduced NMDA receptor expression display behaviors related to schizophrenia. Mohn, A.R., Gainetdinov, R.R., Caron, M.G., Koller, B.H. Cell (1999) [Pubmed]
  42. A comparison of clozapine and haloperidol in hospitalized patients with refractory schizophrenia. Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia. Rosenheck, R., Cramer, J., Xu, W., Thomas, J., Henderson, W., Frisman, L., Fye, C., Charney, D. N. Engl. J. Med. (1997) [Pubmed]
  43. Association of two pertussis toxin-sensitive G-proteins with the D2-dopamine receptor from bovine striatum. Elazar, Z., Siegel, G., Fuchs, S. EMBO J. (1989) [Pubmed]
  44. Haloperidol for acute schizophrenic patients. An evaluation of three oral regimens. Donlon, P.T., Hopkin, J.T., Tupin, J.P., Wicks, J.J., Wahba, M., Meadow, A. Arch. Gen. Psychiatry (1980) [Pubmed]
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