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Chemical Compound Review

AC1NWAK9     3-benzhydryloxy-8-methyl-8...

Synonyms: CCG-38924, HMS501K05, HMS1920G13, HMS2091M15, SPECTRUM1500142, ...
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Disease relevance of benztropine


Psychiatry related information on benztropine


High impact information on benztropine


Chemical compound and disease context of benztropine

  • In an attempt to study his heterogeneity further, the authors measured the responses of 10 patients with tardive dyskinesia to intravenous challenge doses of drugs that facilitate or inhibit acetylcholine transmission (physostigmine or benztropine, respectively) [15].
  • Two atypical inhibitors of the dopamine transporter, benztropine, used in the treatment of Parkinson's disease, and bupropion, used as an antidepressant, show very different psychostimulant effects when compared with another inhibitor, cocaine [16].
  • Twenty-nine inpatients with major psychotic disorders were treated for 14 days with a clinician-determined dose of haloperidol and with either benztropine or placebo given by double-blind random assignment on days 1 through 7 [17].
  • However, benztropine treated patients had a significant increase in tardive dyskinesia compared to their condition during procyclindine treatment, and significantly more anxiety and depression than ethopropazine treated patients [18].
  • Preliminary administration of physostigmine salicylate to patients with tardive dyskinesia had a variable effect, while benztropine mesylate produced no change [19].

Biological context of benztropine


Anatomical context of benztropine


Associations of benztropine with other chemical compounds


Gene context of benztropine

  • Combinatorial synthesis of benztropine libraries and their evaluation as monoamine transporter inhibitors [34].
  • The effect of benztropine on the incidence of dystonia was consistent with other studies, which, when analyzed together, demonstrate the efficacy of anticholinergic prophylaxis [17].
  • We previously prepared a benztropine-based photoaffinity label [125I]-(N-[4-(4'-azido-3'-iodophenyl)butyl]-3alpha-[bis(4'-fluorophenyl)methoxy]tropane, [125I]1, that covalently attached to the 1-2 transmembrane spanning region of the dopamine transporter (DAT) [35].
  • In contrast, prior in vivo reserpine treatment or in vitro addition of benztropine did not affect the depolarization-induced activation of TH [36].
  • B-HT 920, a DA D2 receptor agonist and benztropine, a DA uptake blocker, increased striatal CCK mRNA [37].

Analytical, diagnostic and therapeutic context of benztropine


  1. Benztropine inhibits toxicity of MPTP in mice. Bradbury, A.J., Kelly, M.E., Costall, B., Naylor, R.J., Jenner, P., Marsden, G.D. Lancet (1985) [Pubmed]
  2. MPTP-induced duodenal ulcers in rat. Prevention by reuptake blockers for serotonin and norepinephrine, but not dopamine. Keshavarzian, A., Wibowo, A., Gordon, J.H., Fields, J.Z. Gastroenterology (1990) [Pubmed]
  3. Anticholinergic challenge and neuroleptic withdrawal. Changes in dyskinesia and symptom measures. Gardos, G., Cole, J.O., Rapkin, R.M., LaBrie, R.A., Baquelod, E., Moore, P., Sovner, R., Doyle, J. Arch. Gen. Psychiatry (1984) [Pubmed]
  4. Priapism treated with benztropine. Greenberg, W.M., Lee, K.K. The American journal of psychiatry. (1987) [Pubmed]
  5. Sinus bradycardia related to the use of benztropine mesylate. Voinov, H., Elefante, V., Mujica, R. The American journal of psychiatry. (1992) [Pubmed]
  6. Adjunctive imipramine in the treatment of postpsychotic depression. A controlled trial. Siris, S.G., Morgan, V., Fagerstrom, R., Rifkin, A., Cooper, T.B. Arch. Gen. Psychiatry (1987) [Pubmed]
  7. Neuroleptic-induced akathisia: propranolol versus benztropine. Adler, L.A., Reiter, S., Corwin, J., Herndal, P., Angrist, B., Rotrosen, J. Biol. Psychiatry (1988) [Pubmed]
  8. Neuroleptic drug effects on cognitive function in schizophrenia. Cleghorn, J.M., Kaplan, R.D., Szechtman, B., Szechtman, H., Brown, G.M. Schizophr. Res. (1990) [Pubmed]
  9. Transport, metabolism, and in vivo population pharmacokinetics of the chloro benztropine analogs, a class of compounds extensively evaluated in animal models of drug abuse. Othman, A.A., Syed, S.A., Newman, A.H., Eddington, N.D. J. Pharmacol. Exp. Ther. (2007) [Pubmed]
  10. Effects of benztropine on behavioral and toxic effects of cocaine: comparison with atropine and the selective dopamine uptake inhibitor 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenyl-propyl)-piperazine. Acri, J.B., Siedleck, B.K., Witkin, J.M. J. Pharmacol. Exp. Ther. (1996) [Pubmed]
  11. Differential binding of tropane-based photoaffinity ligands on the dopamine transporter. Vaughan, R.A., Agoston, G.E., Lever, J.R., Newman, A.H. J. Neurosci. (1999) [Pubmed]
  12. Muscarinic antagonists in the treatment of acquired pendular and downbeat nystagmus: a double-blind, randomized trial of three intravenous drugs. Barton, J.J., Huaman, A.G., Sharpe, J.A. Ann. Neurol. (1994) [Pubmed]
  13. Specific uptake of norepinephrine and dopamine by homogenates of rat cerebral cortex after locus ceruleus lesion. Logan, W.J., Harik, S.I. J. Neurosci. (1982) [Pubmed]
  14. The human dopamine transporter forms a tetramer in the plasma membrane: cross-linking of a cysteine in the fourth transmembrane segment is sensitive to cocaine analogs. Hastrup, H., Sen, N., Javitch, J.A. J. Biol. Chem. (2003) [Pubmed]
  15. Identification of a subgroup of tardive dyskinesia patients by pharmacologic probes. Moore, D.C., Bowers, M.B. The American journal of psychiatry. (1980) [Pubmed]
  16. Gain of function mutants reveal sites important for the interaction of the atypical inhibitors benztropine and bupropion with monoamine transporters. Mortensen, O.V., Amara, S.G. J. Neurochem. (2006) [Pubmed]
  17. The effect of benztropine on haloperidol-induced dystonia, clinical efficacy and pharmacokinetics: a prospective, double-blind trial. Goff, D.C., Arana, G.W., Greenblatt, D.J., Dupont, R., Ornsteen, M., Harmatz, J.S., Shader, R.I. Journal of clinical psychopharmacology. (1991) [Pubmed]
  18. Ethopropazine and benztropine in neuroleptic-induced parkinsonism. Chouinard, G., Annable, L., Ross-Chouinard, A., Kropsky, M.L. The Journal of clinical psychiatry. (1979) [Pubmed]
  19. Deanol acetamidobenzoate treatment in choreiform movement disorders. Tarsy, D., Bralower, M. Arch. Neurol. (1977) [Pubmed]
  20. Evaluation of the blood-brain barrier transport, population pharmacokinetics, and brain distribution of benztropine analogs and cocaine using in vitro and in vivo techniques. Raje, S., Cao, J., Newman, A.H., Gao, H., Eddington, N.D. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  21. Simultaneous evaluation by a double labelling method of drug-induced uptake inhibition and release of dopamine in synaptosomal preparation of rat striatum. Bonnet, J.J., Lemasson, M.H., Costentin, J. Biochem. Pharmacol. (1984) [Pubmed]
  22. Recognition of benztropine by the dopamine transporter (DAT) differs from that of the classical dopamine uptake inhibitors cocaine, methylphenidate, and mazindol as a function of a DAT transmembrane 1 aspartic acid residue. Ukairo, O.T., Bondi, C.D., Newman, A.H., Kulkarni, S.S., Kozikowski, A.P., Pan, S., Surratt, C.K. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  23. Development of a sensitive and specific radioimmunoassay for benztropine. He, H., McKay, G., Midha, K.K. Journal of pharmaceutical sciences. (1993) [Pubmed]
  24. Effect of anti-parkinsonism drugs on gastric emptying and intestinal transit in the rat. Feldman, S., Putcha, L. Pharmacology (1977) [Pubmed]
  25. Intraventricular administration of histidyl-proline-diketopiperazine [Cyclo(His-Pro)] suppresses prolactin secretion and synthesis: a possible role of Cyclo(His-Pro) as dopamine uptake blocker in rat hypothalamus. Jikihara, H., Ikegami, H., Koike, K., Wada, K., Morishige, K., Kurachi, H., Hirota, K., Miyake, A., Tanizawa, O. Endocrinology (1993) [Pubmed]
  26. The effects of benztropine and pargyline on the response of cat carotid chemoreceptors to sodium cyanide, acetylcholine and dopamine [proceedings]. Docherty, R.J. J. Physiol. (Lond.) (1979) [Pubmed]
  27. Actions of trihexyphenidyl and benztropine on squid axon membranes. Wu, C.H., Narahashi, T. J. Pharmacol. Exp. Ther. (1976) [Pubmed]
  28. Comparative effects of benztropine and nomifensine on dopamine uptake and release from striatal synaptosomes. McKillop, D., Bradford, H.F. Biochem. Pharmacol. (1981) [Pubmed]
  29. Different developmental schedules of dopaminergic and noradrenergic neurons in dissociation culture of fetal rat midbrain and hindbrain. Ahnert-Hilger, G., Engele, J., Reisert, I., Pilgrim, C. Neuroscience (1986) [Pubmed]
  30. Effect of benztropine on the diurnal prolactin responses to haloperidol. Nathan, R.S., Perel, J.M., McCarthy, T., Jarrett, D.B. Psychoneuroendocrinology (1985) [Pubmed]
  31. Interactions of benztropine, atropine and ketamine with veratridine-activated sodium channels: effects on membrane depolarization, K+-efflux and neurotransmitter amino acid release. Erecińska, M., Nelson, D., Silver, I.A. Br. J. Pharmacol. (1988) [Pubmed]
  32. Selectivity of antimuscarinic compounds for muscarinic receptors of human brain and heart. Larson, E.W., Pfenning, M.A., Richelson, E. Psychopharmacology (Berl.) (1991) [Pubmed]
  33. Quantification of the dopamine innervation in adult rat neostriatum. Doucet, G., Descarries, L., Garcia, S. Neuroscience (1986) [Pubmed]
  34. Combinatorial synthesis of benztropine libraries and their evaluation as monoamine transporter inhibitors. Pedersen, H., Sinning, S., Bulow, A., Wiborg, O., Falborg, L., Bols, M. Org. Biomol. Chem. (2004) [Pubmed]
  35. Novel tropane-based irreversible ligands for the dopamine transporter. Zou, M.F., Kopajtic, T., Katz, J.L., Wirtz, S., Justice, J.B., Newman, A.H. J. Med. Chem. (2001) [Pubmed]
  36. Characteristics of tyrosine hydroxylase activation by K+-induced depolarization and/or forskolin in rat striatal slices. el Mestikawy, S., Gozlan, H., Glowinski, J., Hamon, M. J. Neurochem. (1985) [Pubmed]
  37. Regulation of cholecystokinin mRNA content in rat striatum: a glutamatergic hypothesis. Ding, X.Z., Mocchetti, I. J. Pharmacol. Exp. Ther. (1992) [Pubmed]
  38. Randomised trial of oral morphine for chronic non-cancer pain. Moulin, D.E., Iezzi, A., Amireh, R., Sharpe, W.K., Boyd, D., Merskey, H. Lancet (1996) [Pubmed]
  39. Rhabdomyolysis complicating rapid intramuscular neuroleptization. Thase, M.E., Shostak, M. Journal of clinical psychopharmacology. (1984) [Pubmed]
  40. A comparative study of haloperidol and chlorpromazine in terms of clinical effects and therapeutic reversal with benztropine in schizophrenia. Theoretical implications for potency differences among neuroleptics. Singh, M.M., Kay, S.R. Psychopharmacologia. (1975) [Pubmed]
  41. 3'- and 4'-chloro-substituted analogs of benztropine: intravenous self-administration and in vitro radioligand binding studies in rhesus monkeys. Woolverton, W.L., Rowlett, J.K., Wilcox, K.M., Paul, I.A., Kline, R.H., Newman, A.H., Katz, J.L. Psychopharmacology (Berl.) (2000) [Pubmed]
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