Tiapride

Abstract

Tiapride is a substituted benzamide derivative with selective dopamine D2-receptor antagonist properties which appears to have preferential affinity for extrastriatal dopamine receptors. Animal and clinical studies show that tiapride has anxiolytic properties but the mechanism of action is uncertain. Results from limited studies indicate that the clinical efficacy of tiapride in the treatment of agitation, aggressiveness, anxiety and sleep disorders in the elderly appears superior to that of placebo, chlorpromazine, lorazepam and meprobamate. Tiapride also exerts a beneficial effect on vigilance and alertness in elderly patients and causes less sedation than chlorpromazine. Tiapride is well tolerated at the dosages recommended for elderly patients. Further well designed comparative studies with newer drugs are needed to determine the relative place of tiapride in the treatment of geriatric agitation, and such studies should also address the quality-of-life benefits for the patient. Additional clinical experience to determine the efficacy of tiapride in elderly patients with more than one disease condition, receiving concomitant medications, and/or with renal impairment is also required. However, despite these current limitations, tiapride may have potentially important applications in this difficult area of clinical medicine.

Aldose Reductase, Oxidative Stress, and Diabetic Mellitus

“…However, one of the major proposed mechanisms for the development of the diabetic complications involves the polyol pathway, which mediates the metabolic and osmotic alterations in many tissues (e.g., neurons, platelets). Increased glucose flux through the polyol pathway has been associated with the pathogenesis of diabetic complications via several potential mechanisms, including sorbitol-osmotic effects, depletion of myoinositol (Kinoshita et al, 1962) and subsequent perturbations in Na + /K + ATPase activity (Greene et al, 1987; Steele et al, 1993), disturbances in cellular redox and free radical defense, increased oxidative, and glycation stress, activation of PKC (Steele et al, 1993; Hamada et al, 2000; Hamada and Nakamura, 2004), nitric oxide (NO)-mediated vascular tone (Tesfamariam et al, 1993), and induction of hyperglycemic pseudohypoxia (Van den Enden et al, 1995; Figure 2). Moreover, polymorphic markers of the human AR gene demonstrate a strong association with a susceptibility to develop diabetic complications.…”

Opposing effects of dopamine antagonism in a motor sequence task—tiapride increases cortical excitability and impairs motor learning

“…Afterwards, CE post-training was assessed. The complete experimental procedure after drug administration took 2–2.5 h, fitting largely into the elimination half-life of tiapride which ranges between 3 and 5 h (Rey et al, 1982; Steele et al, 1993; Dose and Lange, 2000). …”

High-performance liquid chromatographic determination of tiapride and its phase I metabolite in blood plasma using tandem UV photodiode-array and fluorescence detection

“…This drug is an atypical neuroleptic (antipsychotic) agent, a selective dopamine D 2 and D 3 receptor antagonist. It is indicated in the cases of severe agitation and aggressiveness, in the treatment of dyskinesias, movement and tic disorders, sleep disorders, anxiety, severe persistent pain and alcohol abuse and dependence [2][3][4][5]. Absorption, distribution, metabolism and elimination (ADME) of 14 C labelled tiapride in rats, dogs and humans after oral and intramuscular administration were studied [6].…”

“…Absorption, distribution, metabolism and elimination (ADME) of 14 C labelled tiapride in rats, dogs and humans after oral and intramuscular administration were studied [6]. Tiapride is metabolized in humans to a minimum extent, up to 70% of the drug is eliminated unchanged in urine within 24 h [5,6]. Only low concentrations of N-desethyl tiapride and tiapride N-oxide were mentioned in previous communications [5,6].…”

“…Tiapride is metabolized in humans to a minimum extent, up to 70% of the drug is eliminated unchanged in urine within 24 h [5,6]. Only low concentrations of N-desethyl tiapride and tiapride N-oxide were mentioned in previous communications [5,6]. No phase II tiapride metabolites were detected in excretes [3,[5][6][7].…”