Download PDF
Pharmacopsychiatry 2000; 33(1): 19-27
DOI: 10.1055/s-2000-7964
Review
Georg Thieme Verlag Stuttgart ·New York

The Benzamide Tiapride: Treatment of Extrapyramidal Motor and Other Clinical Syndromes

M. Dose1 , H. W. Lange2
  • 1Psychiatric District Hospital, Taufkirchen, Germany
  • 2Neurological Therapy Centre (NTC), Cologne, Germany
Further Information

Publication History

Publication Date:
31 December 2000 (online)

Also available at
    Permissions and Reprints

The benzamide derivative tiapride (Tiapridex®, Synthelabo) has a highly selective antagonistic effect on striatal adenylate cyclase-independent dopamine-2 receptors. Its in vitro binding affinity is especially high for dopamine receptors which have been sensitized by pre-incubation with dopamine. The involvement of altered dopamine receptor sensitivity in several extrapyramidal dys- and hyperkinesia has been hypothesized. By its high affinity for these receptors, without any affinity for other neurotransmitter receptors of the brain, tiapride is especially well suited for the treatment of movement disorders related to functional dopamine hyperactivity. Even at higher doses, tiapride does not exceed a D2-receptor occupancy of 80 %, which is in accordance with the finding that tiapride rarely causes acute extrapyramidal syndromes and has, up to now, never implicated in inducing tardive dyskinesias. On the contrary, clinical studies demonstrate its excellent efficacy in neuroleptic-induced tardive dyskinesia, L-Dopa-induced dyskinesias, psychomotor agitation in geriatric patients and choreatic movement disorders. Since tiapride is not available in the USA as yet, most of the studies concerning tiapride have been carried out in Europe. In a recent study, based on objective measurements, tiapride effectively controlled choreatic movements in patients suffering from Huntington's disease (HD). Tiapride is well tolerated in daily doses between 300 and 1200 mg. Adverse events are generaily rare and mild.

References

  • 1 Alexander G, Crutcher M, DeLong M. Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, “prefrontal” and “limbic” functions.  Progr. Brain. Res.. 1990;  85 119-146
    PubMedGoogle Scholar
  • 2 Allain H, Soubrane C, Turjanski S, Bonhomme D. Effectiveness of tiapride in behavioral disorders of demented elderly. Abstract XXIst CINP Glasgow, Scotland 1998, July 12 - 16
    Google Scholar
  • 3 Auberger S, Greil W, Rüther E. Tiapride in the treatment of tardive dyskinesia. A double- blind study.  Pharmacopsychiatry. 1985;  18 61-62
    PubMedGoogle Scholar
  • 4 Bischoff S, Bittiger H, Delini-Stula A, Ortmann R. Septohippocampal system: target for substituted benzamides?.  Europ. J. Pharmacol.. 1982;  79 225-232
    PubMedGoogle Scholar
  • 5 Borison R L, Diamond B I. Neuropharmacology of the Extrapyramidal System.  J. Clin. Psychiatry. 1987;  49 7-12
    PubMedGoogle Scholar
  • 6 Buruma O JS, Roos R AC, Bruyn G W, Kemp B, van der Velde E A. Tiapride in the treatment of tardive dyskinesia.  Acta neuro. scand.. 1982;  65 38-44
    PubMedGoogle Scholar
  • 7 Casey D E, Keepers G A. Neuroleptic side-effects: acute extrapyramidal syndromes and tardive dyskinesia. In: Casey DE, Vibeke-Christiansen A, editors Psychopharmacology: Current Trends. Berlin, New York, London; Springer 1988: 74-93
    Google Scholar
  • 8 Casey D E. Tardive dyskinesia: pathophysiology. In: Bloom FE, Kupfer DJ, editors. Psychopharmacology: the fourth generation of progress. New York; Raven Press 1995: 1497-1502
    Google Scholar
  • 9 Casey D E. Extrapyramidal syndromes.  CNS Drugs. 1996;  5 1-12
    PubMedGoogle Scholar
  • 10 Chivers J K, Gommeren W, Leysen J E, Jenner P, Marsden C D. Comparison of the in-vitro receptor selectivity of substituted benzamide drugs for brain neurotransmitter receptors.  J. Pharm. Pharmacol.. 1988;  40 415-421
    PubMedGoogle Scholar
  • 11 Conrad B. Pathophysiologie der Bewegungsstörungen. In: Conrad B, Ceballos-Baumann AO, Hrsg. Bewegungsstörungen in der Neurologie. Stuttgart, New York; Thieme Verlag 1996: 11-29
    Google Scholar
  • 12 Gerfen C R. The neostriatal mosaic: multiple levels of compartimental organisation.  Trends. Neurosci.. 1992;  15 133-139
    CrossrefPubMedGoogle Scholar
  • 13 Greil W, Auberger A, Haag H, Rüther E. Tiapride: effect on tardive dyskinesia and on prolactin plasma concentrations.  Neuropsychobiol.. 1985;  14 17-22
    PubMedGoogle Scholar
  • 14 Gutzmann H, Kühl K P, Kanowski S, Khan-Boluki J. Measuring the efficacy of psychopharmacological treatment of psychomotoric restlessness in dementia: Clinical evaluation of tiapride.  Pharmacopsychioat.. 1997;  30 6-11
    PubMedGoogle Scholar
  • 15 Hamada I, DeLong M R. Excitotoxic acid lesions of the primate subthalamic nucleus result in reduced pallidal neuronal activity during active holding.  J. Neurophysiol.. 1992;  68 1859-1862
    PubMedGoogle Scholar
  • 16 Justin-Besancon L, Laville C, Margarit J, Thominet M. Constitution chimique et propriété biologiques d'o-anisamides substitué à fonction alkylsulfone.  CR Acad. Sci. (Paris). 1974;  279 375-376
    PubMedGoogle Scholar
  • 17 Kane J M. Spätdyskinesien: Prävalenz, Inzidenz und Risikofaktoren. In: Hinterhuber H, Kulhanek F, Fleischhacker WW, editors. Kombination therapeutischer Strategien bei schizophrenen Erkrankungen. Wiesbaden; Vieweg-Verlag/Braunschweig 1990: 181-193
    Google Scholar
  • 18 Klepel H, Gebelt H, Koch R D, Tzenow H. Die Behandlung extrapyramidaler Hyperkinesen im Kindesalter mit Tiaprid.  Psychiat. Neurol. med. Psychol.. 1988;  40 516-522
    PubMedGoogle Scholar
  • 19 Lange H W, Belemann C, Brandenbusch I, Maurer M, Bauer B. Tiapride treatment of Huntington's chorea. Abstract. Workshop of the World Research Group on Huntington's chorea. Boston. 1993
    Google Scholar
  • 20 Lange H W. Chorea Huntington: Klinik, Therapie und Familienbetreuung. In: Huffmann G, Braune HJ, Henn KH, editors Extrapyramidal-motorische Erkrankungen. Einhorn-Presse Verlag 1994: 494-505
    Google Scholar
  • 21 Lange H W, Berlemann C, Brandenbusch I, Maurer M, Bauer B. Triapride treatment of Huntington's chorea. Unpublished data on file 1996
    Google Scholar
  • 22 Leenders K L, Blauth-Eckmeyer E. PET study with the benzamide Tiapride.  Eur. Psychiatry. 1996;  11 416
    CrossrefPubMedGoogle Scholar
  • 23 L'Hermitte F, Signoret J L, Agit Y. Etude des effets d'une molécule originale, le tiapride, dans le traitment des mouvement anomaux d'origine extrapyramidale.  Sem. Hop.. 1977;  53 9-15
    PubMedGoogle Scholar
  • 24 Liebermann J, Kane J M, Woerner M, Weinhold P, Basavaraju N, Kurucz J, Bergmann K. Prevalence of tardive dyskinesia in elderly samples.  Psyhcopharmacol. Bull.. 1984;  20 382-386
    PubMedGoogle Scholar
  • 25 Liebermann J, Saltz B, Johns C A, Pollack S, Borenstein M, Kane J. The effects of clozapine on tardive dyskinesia.  Brit. J. Psychiatry. 1991;  158 503-510
    PubMedGoogle Scholar
  • 26 Ljungberg T, Apicella P, Schultz W. Responses of monkey dopamine neurons during learning of behavioral reactions.  J. Neurophysiol.. 1992;  67 145-163
    PubMedGoogle Scholar
  • 27 Miller B. Behandlung von psychomotorischer Unruhe bei zentral entwicklungsgestörten Kindern mit Tiaprid. In: Nissen G, editor Therapeutische Probleme bei psychomotorisch unruhigen Kindern. New York; Thieme Verlag/Stuttgart 1982: 56-69
    Google Scholar
  • 28 Murphy D J, Shaw G K, Clarke I. Triapride and chlormethiazole in alcohol withdrawal: a double-blind trial.  Alc. & Alcoholism. 1983;  18 227-237
    PubMedGoogle Scholar
  • 29 Nordstroem A L, Wiesel F A, Farde L. PET analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine: relation to EPS.  Arch. Gen. Psych.. 1992;  49 538-544
    PubMedGoogle Scholar
  • 30 Peters D H, Faulds D. Tiapride - a review of its pharmacology and therapeutic potential in the management of alcohol dependence syndrome.  Drugs. 1994;  47 1010-1032
    CrossrefPubMedGoogle Scholar
  • 31 Price P, Parkes J D, Marsden C D. Tiapride in Parkinson's disease.  Lancet. 1978;  48 1106
    PubMedGoogle Scholar
  • 32 Przuntek H, Baumgarten F, Kohlhepp W, Koch M. Extrapyramidale Erkrankungen (außer Parkinson Syndrom). In: Flügel KA, editor. Neurologische und psychiatrische Therapie. Erlangen; Perimed-Verlag. 1987: 395-422
    Google Scholar
  • 33 Rust M. Anwendung von Tiaprid bei persistierenden Spätdyskinesen als Folge einer Neuroleptika-Behandlung.  Münch. Med. Wschr.. 1983;  21 461-462
    PubMedGoogle Scholar
  • 34 Roos R AC, de Haas E JM, Buruma O JS, de Wolff F A. Pharmacokinetics of tiapride in patients with tardive dyskinesia and Huntington's disease.  Europ. J. Clin. Pharmacol.. 1986;  31 191-194
    CrossrefPubMedGoogle Scholar
  • 35 Remschmidt H. Psychiatrie der Adoleszenz. Stuttgart, New York; Georg Thieme Verlag 1992
    Google Scholar
  • 36 Rothenberger A, Eggers C. The influence of tiapride on the ERPs of children with multiple tics. In: Rothenberger A Event-related potentials in children (Developments in Neurology, vol. 6). Amsterdam; R. Elsevier 1982
    Google Scholar
  • 37 Sedvall G. The current status of PET scanning with respect to schizophrenia.  Neuropsychopharmacol.. 1992;  7 41-54
    PubMedGoogle Scholar
  • 38 Shaw G K, Majumdar S K, Waller S, McGarvie J, Dunn G. Tiapride in the long-term management of alcoholics of anxios or depressive temperament.  Br. J. Psychiatry.. 1987;  150 164-168
    PubMedGoogle Scholar
  • 39 Spargo E I, Everall P, Lantos P L. Neuronal loss in the hippocampus in Huntington's disease: a comparison with HIV infection.  J. Neurol. Neurosurg. Psychiat.. 1993;  56 487-491
    PubMedGoogle Scholar
  • 40 Steele J, Faulds D, Sorkin E M. Tiapride - A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in geriatric agitation.  Drug & Aging. 1993;  3 460-478
    PubMedGoogle Scholar
  • 41 Steinhausen H C. Psychische Störungen bei Kindern und Jugendlichen. München, Wien, Baltimore: Urban & Schwarzenberg 1993
    Google Scholar
  • 42 Storey E, Beal M F. Neurochemical substrates of rigidity and chorea in Huntington's disease.  Brain. 1993;  116 1201-1222
    PubMedGoogle Scholar

Prof. Dr. med. habil. M. Dose

BKH Taufkirchen

Bräuhausstraße 5

D-84416 Taufkirchen

Germany

      >