Disease relevance of FLO 1347

• Tiapride in Parkinson's disease [1].
• Tiapride-induced torsade de pointes [2].
• Tiapride in the treatment of tardive dyskinesia: a clinical and biochemical study [3].
• Tiapride, an atypical neuroleptic agent, is a selective dopamine D2-receptor antagonist with little propensity for causing catalepsy and sedation [4].
• Nevertheless, other mechanisms may be involved, for the evolution of individual parkinsonian and dyskinesia scores is not necessarily opposite: the tiapride-induced parkinsonism was generally acceptable and in two cases, the dyskinesia scores were reduced without an increase in parkinsonism [5].

Psychiatry related information on FLO 1347

• Cataplexy relieved by tiapride [6].
• Tiapride proved better (usually at statistically highly significant levels) than placebo at promoting: abstinence, self-esteem, and satisfaction with life situations; and at reducing: alcohol consumption, use of health service resources, and levels of neuroticism [7].
• Tiapride in 12 Huntington's disease patients [8].
• Changes produced in dopamine (DA) activity, by administration of the DA-antagonists metoclopramide (10 mg/kg IM) and tiapride (16 mg/kg IM) and of the DA agonists apomorphine (0.5 and 1 mg/kg IM) and bromocriptine (8 mg/kg orally), specifically modified predatory behavior in the ferret [9].
• Measuring the efficacy of psychopharmacological treatment of psychomotoric restlessness in dementia: clinical evaluation of tiapride [10].

High impact information on FLO 1347

• The findings suggest a pharmacogenetic influence of DRD2 E8 genotype on tiapride efficacy in alcohol withdrawal [11].
• Haloperidol showed the most potent relative intensity of catalepsy, followed by aprindine, metoclopramide, tiapride, amiodarone and procaine, in that order [12].
• Luciferase expression in this cell line was modified in a dose dependent manner with dopamine receptor agonists (N-propylapomorphine > apomorphine > quinpirole > dopamine) and antagonists (spiperone > (+)-butaclamol > D0710 > (-)-sulpiride > tiapride > remoxipride), according to their rank order of potency in binding and cAMP accumulation studies [13].
• Tiapride, a D2 antagonist that lacks antipsychotic activity, was also included [14].
• Remarkably, all drugs used in this study, including tiapride, down-regulated the levels of both D1 and D5 mRNAs in the prefrontal cortex by 30% to 60% compared with a vehicle control group, whereas mRNAs in the neostriatum were not affected [15].

Chemical compound and disease context of FLO 1347

• L-dopa-induced respiratory disturbance in Parkinson's disease suppressed by tiapride [16].
• 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 [17].
• Tourette syndrome: efficient treatment with ziprasidone and normalization of body weight in a patient with excessive weight gain under tiapride [18].
• BACKGROUND: The benzamide tiapride, a selective dopamine D2/D3-receptor antagonist, can be used effectively in children to treat tic disorders and stuttering [19].
• The effects of tiapride on the convulsive seizures induced by pentylenetetrazole, strychnine, picrotoxin and bemegride, and on electric seizure are reported and compared with those of sulpiride, chlorpromazine, haloperidol and reserpine [20].

Biological context of FLO 1347

• Furthermore, there are indications that tiapride increases platelet counts [21].
• Single oral dose pharmacokinetics of tiapride in patients with Huntington's disease [22].
• However, despite these current limitations, tiapride may have potentially important applications in this difficult area of clinical medicine [23].
• The IC50 values of tiapride, sulpiride and haloperidol were estimated as follows: 1440, 132 and 0.295 microM for D-1; 45.8, 8.8 and 0.004 microM for D-2; greater than 100, greater than 100 and 0.64 microM for D-3; 11.7, 2.88 and 0.0044 microM for D-4, respectively [24].
• Tiapride-induced chronic hyperprolactinaemia: interference with the human menstrual cycle [25].

Anatomical context of FLO 1347

• The same drug treatments produced less uniform effects in the neostriatum than in the cortex: clozapine and olanzapine failed to significantly elevate either D2-long or D2-short receptor messages in this structure unlike all other drugs, including tiapride [14].
• Metoclopramide and tiapride failed to modify either response, failed to antagonise a relaxation to phenylephrine at alpha 1 sites in the same tissue, and failed to modify the contractions caused by dopamine and phenylephrine at an alpha 1-adrenoceptor site in the pyloric sphincter [26].
• To determine the affinity of tiapride to D-1, D-2, D-3 and D-4 subtypes of dopamine (DA) receptors, inhibitory effects of tiapride on [3H]-cis-flupenthixol, [3H]spiperone and [3H]N-propylapomorphine binding were examined in the rat striatum and bovine caudate nucleus membranes and compared to those of sulpiride and haloperidol [24].
• These results are compatible with the hypothesis that tiapride influences the neuroendocrine system [27].
• Both electroacupuncture (EA) and tiapride (icv 400 micrograms/rabbit) enhanced the beta-endorphin-like immunoreactive substance (beta-EPIS) level in cerebrospinal fluid (CSF) measured by radioimmunoassay (RIA) [28].

Associations of FLO 1347 with other chemical compounds

• Oxiperomide and tiapride are dopamine receptor antagonists claimed to have "antidyskinetic" properties in animal models and the clinic [29].
• Ketanserin (1 mg/kg i.p.), a 5-HT2 antagonist, attenuated the effect of tiapride on the second phase but not on the first phase [30].
• The effects of tiapride (100 mg/kg p.o.) on both phases of the formalin test in normal mice were abolished by pretreatment with p-chlorophenylalanine (800 x 2 mg/kg p.o.), a 5-hydroxytryptamine (5-HT) depletor, or pindolol (1 mg/kg i.p.), a 5-HT1 antagonist, but were scarcely affected by 3-tropanyl-indole-3-carboxylate, a 5-HT3 antagonist [30].
• Determination of sultopride and tiapride in serum by gas chromatography using a surface ionisation detector [31].
• Treatment of alcohol withdrawal: tiapride and carbamazepine versus clomethiazole. A pilot study [32].

Gene context of FLO 1347

• This study on the antinociceptive mechanism of action of tiapride (that blocks painful neuropathy in diabetic patients) has led us to hypothesize that the drug attenuates pain transmission through an indirect activation of central 5-HT1 and 5-HT2 receptors [30].
• Five consecutive 5 ml fractions of CSF were drawn from control and tiapride-treated subjects [33].
• 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) [17].
• Tiapride induced an increase of prolactin plasma levels, on the average, from 1,195 to 2,179 microIU/ml (p less than 0.01) [34].
• A patient with Huntington's disease developed acute dystonia whilst treated with tiapride [35].

Analytical, diagnostic and therapeutic context of FLO 1347

• The patients' mental conditions significantly improved while they were taking tiapride, and did not appreciably deteriorate after treatment was discontinued [3].
• Effects of tiapride on electroencephalograms and cognitive functions in the elderly [36].
• This method is applicable to pharmacokinetic studies and therapeutic drug monitoring of sultopride and tiapride [31].
• This was a retrospective study to examine the efficacy, practicability and medical safety of a combination of tiapride and unretarded (fast acting formula) carbamazepine in the treatment of alcohol withdrawal syndrome [37].
• In a placebo-controlled double-blind crossover study of 21 patients chronically treated with neuroleptics and suffering from tardive dyskinesia, tiapride (600 mg/day, mean plasma level: 682 ng/ml) exhibited a transient efficacy during 12 weeks of treatment, most distinct in the 6th week (p less than 0.01) [34].

References