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
-
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
-
3
Auberger S, Greil W, Rüther E.
Tiapride in the treatment of tardive dyskinesia. A double- blind study.
Pharmacopsychiatry.
1985;
18
61-62
-
4
Bischoff S, Bittiger H, Delini-Stula A, Ortmann R.
Septohippocampal system: target for substituted benzamides?.
Europ. J. Pharmacol..
1982;
79
225-232
-
5
Borison R L, Diamond B I.
Neuropharmacology of the Extrapyramidal System.
J. Clin. Psychiatry.
1987;
49
7-12
-
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
-
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
-
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
-
9
Casey D E.
Extrapyramidal syndromes.
CNS Drugs.
1996;
5
1-12
-
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
-
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
-
12
Gerfen C R.
The neostriatal mosaic: multiple levels of compartimental organisation.
Trends. Neurosci..
1992;
15
133-139
-
13
Greil W, Auberger A, Haag H, Rüther E.
Tiapride: effect on tardive dyskinesia and on prolactin plasma concentrations.
Neuropsychobiol..
1985;
14
17-22
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
21 Lange H W, Berlemann C, Brandenbusch I, Maurer M, Bauer B. Triapride treatment of Huntington's chorea. Unpublished data on file 1996
-
22
Leenders K L, Blauth-Eckmeyer E.
PET study with the benzamide Tiapride.
Eur. Psychiatry.
1996;
11
416
-
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
-
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
-
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
-
26
Ljungberg T, Apicella P, Schultz W.
Responses of monkey dopamine neurons during learning of behavioral reactions.
J. Neurophysiol..
1992;
67
145-163
-
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
-
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
-
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
-
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
-
31
Price P, Parkes J D, Marsden C D.
Tiapride in Parkinson's disease.
Lancet.
1978;
48
1106
-
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
-
33
Rust M.
Anwendung von Tiaprid bei persistierenden Spätdyskinesen als Folge einer Neuroleptika-Behandlung.
Münch. Med. Wschr..
1983;
21
461-462
-
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
-
35 Remschmidt H. Psychiatrie der Adoleszenz. Stuttgart, New York; Georg Thieme Verlag 1992
-
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
-
37
Sedvall G.
The current status of PET scanning with respect to schizophrenia.
Neuropsychopharmacol..
1992;
7
41-54
-
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
-
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
-
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
-
41 Steinhausen H C. Psychische Störungen bei Kindern und Jugendlichen. München, Wien, Baltimore: Urban & Schwarzenberg 1993
-
42
Storey E, Beal M F.
Neurochemical substrates of rigidity and chorea in Huntington's disease.
Brain.
1993;
116
1201-1222
Prof. Dr. med. habil. M. Dose
BKH Taufkirchen
Bräuhausstraße 5
D-84416 Taufkirchen
Germany
