Biomedical subjects

A Vidi

Publications and source records attributed to A Vidi.

15 recordsLinked to original sources

PubMed1991

Evidence that imipramine activates 5-HT1C receptor function.

The anti-immobility effect of imipramine (15 mg/kg) in the forced swimming test in mice was antagonized by the non-selective 5-hydroxytryptamine (5-HT) antagonist, metitepine (0.5 mg/kg), by the 5-HT1C/5-HT2 antagonist, mesulergine (15 mg/kg), and by the dopamine D2 antagonist, d,l-sulpiride (50 mg/kg). These three antagonists did not alter the behaviour of imipramine-treated mice in an open-field and did not reduce imipramine brain levels. The 5-HT2 antagonist, ritanserin (0.06 mg/kg), the 5-HT1A/5-HTB antagonist, l-propranolol (20 mg/kg), and the 5-HT3 antagonists, endo-2,3-dihydro-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-2-oxo-1H- benzimidazole-1-carboxamide hydrochloride (DAU 6215; 0.1 mg/kg) and 1,2,3,9-tetrahydro-9-methyl-3[(2-methyl-1H-imidazol-1-yl)methyl]-4H- carbazol-4-one, HCl.2H2O) (GR 38032F; 0.1 mg/kg), failed to reduce imipramine-induced anti-immobility. Subthreshold doses of 8-hydroxy-2-(di-n-propylamino)tetralin hydrochloride (8-OH-DPAT; 0.5 mg/kg) and imipramine (7.5 mg/kg) did not synergize in reducing immobility. d,l-Sulpiride, but not mesulergine, antagonized the effect of desipramine (15 mg/kg) in the forced swimming test. All compounds were administered i.p. 6 min before imipramine or desipramine, given i.p. 30 min before the testing. Imipramine produced 50% inhibition of [3H]mesulergine binding to 5-HT1C receptors at 10 microM, a concentration below that obtained following i.p. imipramine administration. The results suggest a contribution of 5-HT1C receptors in the mechanism of the imipramine effect in the forced swimming test.

Animals↗

PubMed1988

Safety and pharmacokinetics of mifentidine after increasing oral doses in healthy subjects.

Eight healthy men were each given single oral doses of mifentidine 20, 40 and 80 mg, a new H2-receptor antagonist, in a four-way, double-blind, placebo-controlled, cross-over, dose-proportionality study. No significant objective or subjective effects were noted. Mifentidine showed unusual pharmacokinetic behaviour, producing a significant secondary peak in the drug concentration profile. The plasma AUC of mifentidine increased linearly with dose (r = 0.983). The apparent plasma clearance was 38.1 l.h-1, 31.0 l.h-1, and 47.4 l.h-1 for the 20, 40 and 80 mg doses, respectively, and the corresponding terminal plasma half-lives were 10.3 h, 12.0 h, and 8.6 h. About 20% of the parent drug was excreted in urine over 24 h. The renal clearance (9.41 l/h for 20 mg, 9.5 l/h for 40 mg, and 12.8 l/h for 80 mg mifentidine) indicates that some of the drug was excreted by active tubular secretion. The results indicate that mifentidine is safe after single oral doses up to 80 mg. The pharmacokinetics of the 20 and 40 mg doses were similar, but after 80 mg the total body and renal clearances were significantly greater than after the two lower doses. As the terminal plasma half-life of mifentidine is longer than of other available H2-receptor antagonists, it may have clinical implications for once-a-day therapy of peptic ulcer diseases.

Administration, Oral↗

PubMed1988

Pharmacokinetics of mifentidine after single and multiple oral administration to healthy volunteers.

1. The pharmacokinetics of mifentidine, a new long acting histamine H2-receptor antagonist, were studied using two protocols. 2. In one study, on 5 different days six normal male subjects were given 2.5, 5, 10, or 20 mg mifentidine or placebo orally 60 min before starting a 3 h continuous gastric aspiration during which time blood samples were taken for measurement of mifentidine concentration. 3. The area under the curves of mifentidine plasma levels (AUC) vs time for the four doses was linearly related to the dose for each individual subject (r = 0.972, P less than 0.001). After doses of 2.5, 5, 10 and 20 mg, mifentidine reduced hydrogen ion output by respectively 36, 37, 60 and 75% and secretory volume by 1, 17, 40, and 47%. The effects at the two highest doses were statistically significant. AUC was correlated positively with the percentage reduction in hydrogen ion output (r = 0.802, P less than 0.001) and volume (r = 0.834, P less than 0.001) over a 3 h period. 4. In the second study, the pharmacokinetics were evaluated after once-daily treatment for 14 days in seven subjects given 10 mg and in seven others subjects given 20 mg. 5. After multiple dosing, renal clearance was similar for the two doses (11.6 +/- 2.11 l h-1 for the low dose and 17.0 +/- 2.0 l h-1 for the high dose). Plasma half-life (t1/2 lambda 2) was 16.0 +/- 3.0 h after the 10 mg dose and 11.9 +/- 1.2 h after 20 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1986

Discontinuous oral absorption of cimetropium bromide, a new antispasmodic drug.

The pharmacokinetic profiles of cimetropium bromide, after either intravenous injection of 10 mg or oral ingestion of 200 mg, were determined in eight healthy volunteers. After intravenous administration, the plasma levels and urinary excretion indicated that the drug is distributed and eliminated at a rapid rate (terminal half-life, 50 +/- 8 min) and that urinary excretion is not the exclusive route of elimination (46 +/- 2%) of the administered dose). After oral administration, a low percentage of the drug is absorbed (1-4% of the administered dose), however, the amount is sufficient for therapeutic effect. The absorption is discontinuous, with two distinct phases, and ends abruptly during the second phase.

Administration, Oral↗

PubMed1986