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Bromperidol, a new butyrophenone neuroleptic: A review

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Abstract

This review compares and contrasts the preclinical pharmacology of bromperidol with another butyrophenone neuroleptic, haloperidol, and the phenothiazine neuroleptic chlorpromazine. Its pharmacokinetics, biotransformation, and safety in several laboratory animal species are also summarized. These preclinical data support its use as an antipsychotic agent and show that it is well absorbed following oral administration with an apparent elimination half-life of approximately 24 h, supporting a once-daily dose regimen. Animal toxicity (including acute- and multiple-dose toxicology and reproductive and mutagenicity studies) show that bromperidol is well tolerated.

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References

  • Abrams L, Chaikin P, Tischio J, Killinger J, Weintraub H (1980) Comparative bioavailability and pharmacokinetics of bromperidol in dogs following oral multiple-dose administration. Pharm Sci 10:97 (abstract)

    Google Scholar 

  • Andén NE, Stock G (1973) Effect of clozapine on the turnover of dopamine in the corpus striatum and in the limbic system. J Pharm Pharmacol 25:346–348

    Google Scholar 

  • Bartholini G (1976) Differential effect of neuroleptic drugs on dopamine turnover in the extrapyramidal and limbic system. J Pharm Pharmacol 28:429–433

    Google Scholar 

  • Bennett Jr JP, Snyder SH (1975) Stereospecific binding of d-lysergic acid diethylamide (LSD) to brain membranes: Relationship to serotonin receptors. Brain Res 94:523–544

    Google Scholar 

  • Burt DR, Creese I, Snyder SH (1976) Properties of 3H-dopamine binding associated with dopamine receptors in calf brain membranes. Mol Pharmacol 12:800–812

    Google Scholar 

  • Carlsson A, Lindqvist M (1963) Effect of chlorpromazine and haloperidol on formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta Pharmacol Toxicol (Copenh) 20:140–144

    Google Scholar 

  • Chasseaud LF (1978) Metabolic fate of bromperidol in humans: Comparison with rats and dogs. Acta Psychiatr Belg 78:51–63

    Google Scholar 

  • Creese I, Burt DR, Snyder SH (1975) Dopamine receptor binding: Differention of agonist and antagonist states with 3H-dopamine and 3H-haloperidol. Life Sci 17:993–1001

    Google Scholar 

  • Creese I, Burt DR, Snyder SH (1976a) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192:481–483

    Google Scholar 

  • Creese I, Feinberg AP, Snyder SH (1976b) Butyrophenone influences on the opiate receptor. Eur J Pharmacol 36:231–235

    Google Scholar 

  • Crow TJ, Deakin JFW, Longden A (1977) The nucleus accumbens: Possible site of antipsychotic action of neuroleptic drugs? Psychol Med 7:213–221

    Google Scholar 

  • Ellinwood Jr EH (1967) Amphetamine psychosis. I. Description of the individuals and process. J Nerv Ment Dis 144:273–283

    Google Scholar 

  • Haase HJ, Kaumeier S, Schwarz H, Gundel A, Linde OK, Maetz H, Scheel R, Stripf A, Stripf L (1978) Open study with bromperidol (C-C2489), a new neuroleptic for the determination of the neuroleptic threshold and the neuroleptic-therapeutic range. Pharmakopsychiatrie 11:81–85

    Google Scholar 

  • Hermans BFK, Van Daele P, Van de Westeringh C, Van der Eycken C, Boey J, Janssen PAJ (1965) 4-Substituted piperidines. II. Reaction of 1-benzyl-4-cyano-4-t-aminopiperidines with organo-metallic compounds. J Med Chem 8:851–855

    Google Scholar 

  • Hermans BFK, Van Daele P, Van de Westeringh C, Van der Eycken C, Boey J, Janssen PAJ (1966) 4-Substituted piperidines. III. Reduction of 1-benzyl-4-cyano-4-t-aminopiperidines with lithium aluminium hydride. J Med Chem 9:49–52

    Google Scholar 

  • Heykants J, Meuldermans W, Michiels M (1978) Absorption, excretion and metabolism of oral bromperidol in rats and dogs. Eur J Drug Metab Pharmacokinet 2:111–117

    Google Scholar 

  • Hyttel J (1978) Effects of neuroleptics on 3H-haloperidol and 3H-cis(Z)-flupenthixol binding and on adenylate cyclase activity in vitro. Life Sci 23:551–556

    Google Scholar 

  • Janssen PAJ (1961a) Comparative pharmacologic data on six new basic 4′-fluorobutyrophenone derivatives: Haloperidol, haloanisone, triperidol, methylperidide, haloperidide, and dipiperone. 1. Arzneim Forsch 11:819–824

    Google Scholar 

  • Janssen PAJ (1961b) Comparative pharmacologic data on six new basic 4′-fluorobutyrophenone derivatives: Haloperidol, haloanisone, triperidol, methylperidide, haloperidide, and dipiperone. 2. Arzneim Forsch 11:932–938

    Google Scholar 

  • Janssen PAJ (1973) Structure-activity relations (SAR) and drug design as illustrated with neuroleptic agents. In: Calallito, CJ (ed) International encyclopedia of pharmacology and therapeutics. Pergamon, Oxford, pp 37–73

    Google Scholar 

  • Janssen PAJ, Van Bever WFM (1975) Advances in the search for improved neuroleptic drugs. Curr Dev Psychopharmacol 2:167–184

    Google Scholar 

  • Janssen PAJ, Van Bever WFM (1977) The butyrophenones and diphenylbutylamines. In: Usdin C, Forrest I (eds) Psychotherapeutic drugs, vol II. Marcel Dekker, New York, pp 869–921

    Google Scholar 

  • Janssen PAJ, Van Bever WFM (1978) Structure-activity relationships of the butyrophenones and diphenyl-butylpiperidines. In: Iversen LL, Iversen SO, Snyder SH (eds) Handbook of psychopharmacology, vol 10. Plenum, New York, pp 1–35

    Google Scholar 

  • Janssen PAJ, Niemegcers CJE, Jageneau AHM (1960) Apomorphine antagonism in rats. Arzneim Forsch 10:1003–1005

    Google Scholar 

  • Janssen PAJ, Niemegeers CJE, Schellekens KHL (1965a) Is it possible to predict the clinical effects of neuroleptic drugs (major tranquilizers) from animal data? I. Neuroleptic activity spectra for rats. Arzneim Forsch 15:104–117

    Google Scholar 

  • Janssen PAJ, Niemegeers CJE, Schellekens KHL (1965b) Is it possible to predict the clinical effects of neuroleptic drugs (major tranquilizers) from animal data? II. Neuroleptic activityspectra for dogs. Arzneim Forsch 15:1196–1206

    Google Scholar 

  • Janssen PAJ, Niemegeers CJE, Schellekens KHL, Lenaerts FM (1967) Is it possible to predict the clinical effects of neuroleptic drugs (major tranquilizers) from animal data? IV. An improved experimental design for measuring the inhibitory effects of neuroleptic drugs on amphetamine- or apomorphine-induced chewing and agitation in rats. Arzneim Forsch 17:841–854

    Google Scholar 

  • Janssen PAJ, Van de Westeringh C, Jageneau AHM, Demeen PJA, Hermans BKF, Van Dael GHP, Schellekens KHL, Van der Eycken CAM, Niemegeers CJE (1959) Chemistry and pharmacology of CNS depressants related to 4-(4-hydroxy-4-phenyl-1-(piperidino)-butyrophenone. I. Synthesis and screening data in mice. J Med Pharmacol Chem 1:281–297

    Google Scholar 

  • Laduron PM (1980) Dopamine receptor: From an in vivo concept towards a molecular characterization. Trends Pharmacol Sci 1:471–474

    Google Scholar 

  • Leysen JE, Gommeren W, Laduron PM (1978a) Spiperone: A ligand of choice for neuroleptic receptors. 1. Kinetics and characteristics of in vitro binding. Biochem Pharmacol 27:307–316

    Google Scholar 

  • Leysen JE, Niemegeers CJE, Tollenaere JP, Ladnron PM (1978b) Serotonergic component of neuroleptic receptors. Nature 272:168–171

    Google Scholar 

  • Marsboom R (1978) Toxikologische Untersuchungen von Neuroleptika der Butyrophenonreihe und verwandter Substanzen. Int Pharmacopsychiatry (Suppl) 1:3–14

    Google Scholar 

  • Michiels M, Hendriks R, Heykants J (1977) RIA determination of haloperidol and bromperidol: Manual for radioimmunoassay. Janssen Pharmaceutica, Beerse, Belgium

    Google Scholar 

  • Niemegeers CJE, Awouters F, Van Neuten J, de Nollin S, Janssen PAJ (1978a) Protection of rats from compound 48/80-induced lethality: A simple test for inhibitors of mast cell-mediated shock. Arch Int Pharmacodyn Ther 234:164–176

    Google Scholar 

  • Niemegeers CJE, Dubinsky B, Laduron P, McGuire JL (1978b) Bromperidol: Comparative CNS profile of a new neuroleptic in rats and dogs. Fed Proc 37:618 (abstract)

    Google Scholar 

  • Niemegeers CJE, Laduron PM, Janssen PAJ (1978c) Pharmacology and biochemistry of bromperidol. Acta Psychiatr Belg 78:37–50

    Google Scholar 

  • Niemegeers CJE, Lenaerts FM, Artois KSK, Janssen PAJ (1977) Interaction of drugs with apomorphine, tryptamine and norepinephrine. A new in vivo approach: The ATN test in rats. Arch Int Pharmacodyn Ther 227:238–253

    Google Scholar 

  • Niemegeers CJE, Janssen PAJ (1974) Bromperidol, a new potent neuroleptic of the butyrophenone series: Comparative pharmacology of bromperidol and haloperidol. Arzneim Forsch 24:45–52

    Google Scholar 

  • Niemegeers CJE, Janssen PAJ (1979) A systematic study of the pharmacological activities of dopamine antagonists. Life Sci 24:2201–2216

    Google Scholar 

  • Poldinger W, Bures B, Haage H (1977a) Clinical study with bromperidol, a new butyrophenone derivative. Int Pharmacopsychiatry 12:20–24

    Google Scholar 

  • Poldinger W, Bures B, Haage H (1977b) Double-blind study with two butyrophenone derivatives: Bromperidol vs. haloperidol. Int Pharmacopsychiatry 12:184–192

    Google Scholar 

  • Seeman P, Chau-Wong M, Tedesco J, Wong K (1975) Brain receptors for antipsychotic drugs and dopamine: Direct binding assays. Proc Natl Acad Sci USA 72:4376–4380

    Google Scholar 

  • Sidman M (1953) Avoidance conditioning with brief shock and no exteroceptive warning signal. Science 118:157–158

    Google Scholar 

  • Snyder SH (1972) Catecholamines in the brain as mediators of amphetamine psychosis. Arch Gen Psychiatry 27:343–351

    Google Scholar 

  • Swazey JP (1974) Chlorpromazine in psychiatry: A study of therapeutic innovation. MIT Press, Cambridge, MA

    Google Scholar 

  • Tishio J, Chaikin P, Abrams L, Hetyei N, Patrick J, Weintraub H, Collins D, Chasin M, Wesson D, Abuzzahab F (1982) Comparative bioavailability and pharmacokinetics of bromperidol in schizophrenic patients following oral administration. J Clin Pharmacol 22:16 (abstract)

    Google Scholar 

  • Tischio J, Hetyei N, Patrick J, Killinger J (1981) Determination of bromperidol in human plasma by radioimmunoassay (RIA) methodology. Clin Chem Abstr 27:403

    Google Scholar 

  • Van den Eeckhout E, Belpaire FM, Bogaert BG, De Moerloose P (1980) Radioimmunoassay of bromperidol and haloperidol in human and canine plasma. Eur J Drug Metab Pharmacokinet 5:45–48

    Google Scholar 

  • Westerink BHC, Lejeune B, Korf J, Van Praag HM (1977) On the significance of regional dopamine metabolism in the rat brain for the classification of centrally acting drugs. Eur J Pharmacol 42:179–190

    Google Scholar 

  • Wauquier A, Niemegeers CJE (1976) Bromperidol, a new potent neuroleptic of the butyrophenone series: A comparison of the effects of bromperidol and haloperidol in intracranial self-stimulation. Arzneim Forsch 26:1356–1359

    Google Scholar 

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Authors and Affiliations

  1. Research Laboratories, Ortho Pharmaceutical Corporation, 08869, Raritan, NJ, USA

    B. Dubinsky, J. L. McGuire, H. S. Weintraub & B. E. McKenzie

  2. Research Laboratoria, Janssen Pharmaceutica, Beerse, Belgium

    C. J. E. Niemegeers & P. A. J. Janssen

Authors
  1. B. Dubinsky
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  2. J. L. McGuire
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  3. C. J. E. Niemegeers
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  4. P. A. J. Janssen
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  5. H. S. Weintraub
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  6. B. E. McKenzie
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Dubinsky, B., McGuire, J.L., Niemegeers, C.J.E. et al. Bromperidol, a new butyrophenone neuroleptic: A review. Psychopharmacology 78, 1–7 (1982). https://doi.org/10.1007/BF00470578

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  • DOI: https://doi.org/10.1007/BF00470578

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