Reference

Pharmacokinetics of single intravenous and oral doses of dolasetron mesylate in healthy elderly volunteers

Pharmacokinetics of single intravenous and oral doses of dolasetron mesylate in healthy elderly volunteers. Dempsey, Ellen; Bourque, Stephane; Spenard, Jean; Landriault, Helene (Departments Biopharmaceutics and Clinical Research, Hoechst Marion Roussel, Laval, QC H7S 2A4, Can.).Several substances are used for example 127951-99-9 and 115956-13-3 which are their cas registry numbers. Journal of Clinical Pharmacology, 36(10), 903-910 (English) 1996 Lippincott-Raven. CODEN: JCPCBR. ISSN: 0091-2700. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Dolasetron mesylate (MDL 73,147EF, Anzemet; Hoechst Marion Roussel, Laval, Canada) is a 5-HT3 receptor antagonist undergoing clin. evaluation for use as an antiemetic agent. The pharmacokinetics of dolasetron and its reduced metabolite (MDL 74,156) were studied after administration of single i.v. and oral doses of dolasetron mesylate 2.4 mg/kg in 18 healthy elderly subjects. Expressed as the dolasetron base, this dose was 1.8 mg/kg. Dolasetron was rapidly metabolized to the reduced metabolite, which appeared in plasma within 10 min after i.v. or oral administration. The mean half-life (t1/2) of dolasetron was 0.24 h after i.v. administration and 0.50 h after oral administration. The pharmacokinetic parameters of the reduced metabolite were similar after i.v. and oral administration. The apparent abs. bioavailability of the reduced metabolite was 89%, and it had an elimination t1/2 of approx. 7 h and an apparent vol. of distribution (Vdb) of 4.69 L/kg. Dolasetron was not detected in urine. Metabolites were excreted in urine almost completely within 24 h of administration. The primary metabolite detected in urine was the [+]-enantiomer of the reduced metabolite, which accounted for 25.35% (± 7.79%) and 18.88% (± 7.65%) of the i.v. and oral doses, resp. Hydroxylated metabolites accounted for 5% or less of the total dose via either route. The pharmacokinetics of the reduced metabolite after single i.v. or oral doses in elderly volunteers were consistent with pharmacokinetics obsd. in both young healthy men and cancer patients receiving high-dose cisplatin chemotherapy. Dosage adjustments of dolasetron mesylate on the basis of age do not appear to be necessary. .

The effect of 5-HT3 receptor antagonists on the discriminative stimulus effects of amphetamine

The effect of 5-HT3 receptor antagonists on the discriminative stimulus effects of amphetamine. Moser, Paul C. (Marion Merrell Dow Res. Inst., Strasbourg 69009, Fr.). Eur. J. Pharmacol., 212(2-3), 271-4 (English) 1992. CODEN: EJPHAZ. ISSN: 0014-2999. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The discriminative stimulus induced in rats by amphetamine has previously been shown to be due to raised mesolimbic dopamine levels. As 5-HT3 receptor antagonists have been shown to inhibit hyperactivity resulting from raised mesolimbic dopamine levels, the present study examd. their effects against the amphetamine discriminative stimulus. None of the 5-HT3 receptor antagonists tested (MDL 72222EF, 0.3-10 mg/kg s.c.; MDL 73147EF, 0.3-10 mg/kg s.c.; ICS 205-930, 0.01-10.0 mg/kg s.There are some commonly used reagents with their cas registry numbers 99614-01-4 and 115956-13-3 in this article.c.; ondansetron, 0.1-1000 mg/kg s.c.) antagonized the effects of amphetamine in this test. This suggests that 5-HT3 receptors cannot modulate the effects of raised mesolimbic dopamine in pathways involved in the interoceptive effects of amphetamine. .