timiperone and Neoplasms

Carbonyl reductase 1 (CBR1), an enzyme belonging to the short-chain dehydrogenases/reductases family, has been detected in all human tissues. CBR1 catalyzes the reduction of many xenobiotics, including important drugs (e.g. anthracyclines, nabumetone, bupropion, dolasetron) and harmful carbonyls and quinones. Moreover, it participates in the metabolism of a number of endogenous compounds and it may play a role in certain pathologies. Plant polyphenols are not only present in many human food sources, but are also a component of many popular dietary supplements and herbal medicines. Many studies reviewed herein have demonstrated the potency of certain flavonoids, stilbenes and curcuminoids in the inhibition of the activity of CBR1. Interactions of these polyphenols with transcriptional factors, which regulate CBR1 expression, have also been reported in several studies. As CBR1 plays an important role in drug metabolism as well as in the protection of the organism against potentially harmful carbonyls, the modulation of its expression/activity may have significant pharmacological and/or toxicological consequences. Some polyphenols (e.g. luteolin, apigenin and curcumin) have been shown to be very potent CBR1 inhibitors. The inhibition of CBR1 seems useful regarding the increased efficacy of anthracycline therapy, but it may cause the worse detoxification of reactive carbonyls. Nevertheless, all known information about the interactions of polyphenols with CBR1 have only been based on the results of in vitro studies. With respect to the high importance of CBR1 and the frequent consumption of polyphenols, in vivo studies would be very helpful for the evaluation of risks/benefits of polyphenol interactions with CBR1.

Topics: Alcohol Oxidoreductases; Animals; Bupropion; Butanones; Butyrophenones; Daunorubicin; Doxorubicin; Gene Expression Regulation, Enzymologic; Haloperidol; Humans; Indoles; Nabumetone; Neoplasms; Phenylpropionates; Polyphenols; Quinolizines; Substrate Specificity; Xenobiotics

Topics: Administration, Oral; Adult; Antiemetics; Antipsychotic Agents; Butyrophenones; Cisplatin; Female; Humans; Injections, Intravenous; Male; Middle Aged; Neoplasms; Vomiting

A new neuroleptic drug, Timiperone, is able to exert an antiapomorphine effect at doses smaller than cataleptogenic doses. Nineteen patients with urologic malignancy undergoing chemotherapy with cisplatin in combination with other agents were studied for the antiemetic efficacy of Timiperone. Six of 8 patients over 46 years old treated with Timiperone 6 mg/day p.o. from the day before undergoing DDP therapy to the last day of the therapy had no episode of vomiting and 2 patients had a few episodes of emesis (one and two episodes during 5 days of undergoing DDP, respectively). Five patients under 45 years old given Timiperone 6 mg/day by the same method had few episodes of vomiting, but suffered from extrapyramidal symptoms. Finally 6 patients undergoing DDP with Timiperone in combination with trihexyphenidyl suffered no symptoms of catalepsy but sometimes had mild vomiting episodes (1-4 times a day). We would like to propose that in antiemetic therapy with Timiperone for cisplatin-induced nausea and vomiting, a dose of 4.5 mg/day be given from two days before undergoing chemotherapy because of the cumulative effect of Timiperone.

Topics: Adult; Aged; Antiemetics; Butyrophenones; Cisplatin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Testicular Neoplasms; Urinary Bladder Neoplasms; Vomiting