2 results
Clinical management of agitation in the elderly with tiapride
- P.H. Robert, H. Allain
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- Journal:
- European Psychiatry / Volume 16 / Issue S1 / 2001
- Published online by Cambridge University Press:
- 16 April 2020, pp. 42s-47S
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Agitated behaviors such as uncooperativeness with necessary care, motor hyperactivity, and verbal or physical aggression are some of the most commonly reported complications in dementia and organic disorders in elderly subjects. These symptoms present greater clinical challenges and management issues than the cognitive deficits. Antipsychotics are the most commonly used psychotropic agents for treating these types of symptoms.
The aims of this article are to review clinical studies with tiapride, a substituted benzamide, and more specifically to present recent data coming from two double-blind, randomized studies in elderly subjects.
The first study versus melperone was conducted in Germany, with over 176 hospitalized demented patients, and indicated that tiapride was as effective and safe as melperone.
More recently, a multicentre, international, double-blind, three-parallel group study compared a 21-day treatment of tiapride to haloperidol and placebo and included 306 demented elderly patients with agitation and aggressiveness. The results showed that tiapride and haloperidol were significantly effective in the treatment of agitation and aggressiveness compared to placebo. The tiapride safety profile was found to be better than haloperidol for clinical acceptability, particularly for significantly fewer extrapyramidal symptoms in the tiapride group.
The preclinical pharmacologic profile of tiapride
- B. Scatton, C. Cohen, G. Perrault, A. Oblin, Y. Claustre, H. Schoemaker, D.J. Sanger, L. Rouquier, R. Porsolt
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- Journal:
- European Psychiatry / Volume 16 / Issue S1 / 2001
- Published online by Cambridge University Press:
- 16 April 2020, pp. 29s-34S
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Tiapride is a benzamide derivative that has been used successfully in the clinic for a number of years for the treatment of agitation and aggressiveness in elderly patients. Like many substituted benzamides, tiapride specifically blocks dopamine receptors in the brain. It has affinity for dopamine D2 (IC50 = 110–320 nM) and D3 (IC50 = 180 nM) receptors in vitro but lacks affinity for dopamine D1 and D4 receptors and for non-dopaminergic receptors including H1, α1, α2-adrenergic and serotonergic receptors. Tiapride also shows dose-related inhibition of [3H]-raclopride binding in limbic areas and in the striatum of the rat in vivo (ED50 ∼ 20 mg/kg, ip). In microdialysis experiments, tiapride (over the range 10–30 mg/kg, ip) increased extracellular levels of dopamine in the nucleus accumbens and striatum, a reflection of its blockade of postsynaptic dopamine receptors in these brain areas.
In behavioral experiments in rats, lower doses of tiapride (ED50 = 10 mg/kg, ip) antagonised dopamine agonist-induced hyperactivity while higher doses (ED50 = 60 mg/kg, ip) were required to block stereotyped movements.
In addition, doses of tiapride up to 200 mg/kg, ip failed to induce catalepsy, an effect observed with many other drugs which block dopamine receptors. In tests of conditioned behavior in rats, tiapride was found to give rise to an interoceptive stimulus associated with dopamine receptor blockade at doses (ED50 = 2.2 mg/kg, ip) much lower than those producing motor disturbances or sedation (ED50 = 40 mg/kg, ip), in striking contrast to a range of conventional or atypical neuroleptics that produced interoceptive stimulus and sedation at similar doses. Furthermore, the acquisition by rats of a place-learning task in a water maze was not affected by tiapride (over the range 3–30 mg/kg, ip), whereas haloperidol (MED = 0.25 mg/kg, ip) and risperidone (MED = 0.03 mg/kg, ip) impaired performance.
The preclinical pharmacologic and behavioral profile of tiapride suggests that its clinical activity may be due to a selective blockade of dopamine D2 and D3 receptors in limbic brain regions. The results are also consistent with a lack of motor or cognitive side effects.