Disposition and metabolism of buspirone and its metabolite 1-(2-pyrimidinyl)-piperazine in the rat.

After i.v. injection (10 mg/kg) to rats, buspirone is rapidly cleared from blood with a t1/2 (beta) or 30 min.

Plasma pyroglutamic acid levels after oral administration of monosodium glutamate to human volunteers.

Plasma levels of pyroglutamic (PY) and glutamic (GA) acids have been measured after oral administration of monosodium glutamate (MSG) to 6 human volunteers. MSG (43 mg/kg) was administered either after an overnight fast or immediately after a normal meal. In fasting subjects plasma GA peak levels were about 2.

Metabolic and pharmacological studies with N-methyl-N'-methyl-2'-allyl-2-benzoyl-4-chloro-glycinanilide (F 1797).

Three metabolites (F 1756, diazepam and N-desmethyl-diazepam) of N-methyl-N'-methyl-2'-allyl-2-benzoyl-4-chloro-glycinanilide (F 1797), a new potential anxiolytic agent, are formed by N-desmethylation or cyclisation in the rat. They were compared with F 1797 for their antileptazol activity in order to assess their contribution to the effect of the parent compound. F 1756 had little effect in this test.

Notes on buspirone's mechanisms of action.

Buspirone is a novel psychotropic drug with clear anxiolytic activity in man. There are a number of neurochemical differences between buspirone and both neuroleptics and benzodiazepines. Moreover, buspirone is extensively metabolized, and several metabolites are present in the brain together with the parent compound.

Brain levels of tofizopam in the rat and relationship with benzodiazepine receptors.

The effect of tofizopam on 3H-flunitrazepam binding was studied in rat hippocampus and cerebellum. Tofizopam (at a concentration of 10(-7) M) increased 3H-Flu binding through a 30% rise in the Bmax with no modification of Kd in either brain area. Similar results were obtained when the binding was measured in tofizopam (50 mg/kg p.

Species differences in the kinetics and metabolism of fenfluramine isomers.

After single oral doses of racemic fenfluramine to man and animals (male CD-COBS Sprague-Dawley rat, male CD1-COBS mice and male beagle dogs) plasma and/or brain concentrations of the d- and l-isomers and their deethylated metabolite were measured by gas-liquid chromatography. In rat and mouse d-fenfluramine had a longer half-life (T 1/2) and gave a larger area under the curve (AUC) than the l-isomer. These differences were consistent with stereoselective N-deethylation of l-fenfluramine.

Effect of dimethylamino-2-ethoxyimino-2-adamantane (CM 54903), a non-polar dimethylaminoethanol analog, on brain regional cholinergic neurochemical parameters.

CM 54903, a new psychotropic drug with a particular pharmacological profile, produced a widespread but short-lasting decrease in acetylcholine content in rat brain hemispheric regions but not in the midbrain-hindbrain or cerebellum at the dose of 40 mg/kg, i.p. The decrease was most conspicuous in the striatum.

Plasma and brain levels of glutamate and pyroglutamate after oral monosodium glutamate to rats.

Plasma and brain levels of pyroglutamate (Py), a compound connected with the pathway of glutamate (GA) metabolism, were measured in rats after oral administration of monosodium glutamate (MSG) or Py. Oral MSG (1 g/kg) was followed by only a small rise in plasma Py levels. No increase of Py or GA brain levels was observed in these experimental conditions.

Species differences in phenazepam kinetics and metabolism.

The kinetic profiles of phenazepam and its hydroxylated derivative were compared in rat, dog, cat and man after administration of single oral doses of the parent compound. The absorption of phenazepam was reasonably rapid in all the species studied. Blood peak concentrations (Cmax) were reached at 1 h in rats (0.

Antileptazol activity and kinetic of CP 1414 S (7-nitro-2-amino-5-phenyl-3-H-,1,5-benzodiazepine-4-one) in the rat and mouse.

The antileptazol effect of CP 1414 S (7-nitro-2-amino-3-phenyl-3H-1,5-benzodiazepine-4-one) a newly developed 1,5 benzodiazepine, lasts longer in mice than in rats. After intraperitoneal injection (10 mg/kg) brain levels of the drug were higher and persisted for longer in the mouse than in the rat. Although it cannot be excluded tht possible metabolites of CP 1414 S may contribute to the anticonvulsant effect of CP 1414 S, in both species the protective effect correlates well with the brain concentrations of the drug.

Antileptazol activity and kinetics of clobazam and N-desmethyl-clobazam in the guinea-pig.

The kinetic profiles and antileptazol activity of clobazam and its main metabolite were compared to assess the metabolite's contribution to the anticonvulsant activity of clobazam in the guinea-pig. The metabolite was less effective than the parent compound in terms of doses and active brain levels. However, the metabolite formed after clobazam administration accounted for the persistence of antileptazol activity in this animal species.

Determination of plasma and brain concentrations of trazodone and its metabolite, 1-m-chlorophenylpiperazine, by gas-liquid chromatography.

A sensitive and specific gas chromatographic procedure is described for the quantitation of trazodone and its active metabolite, 1-m-chlorophenylpiperazine (mCPP), in plasma and brain. After addition of internal standards, the samples were extracted with benzene and the extracts divided into two portions. One portion was evaporated to dryness, and residue dissolved in methanol and the solution injected into a gas chromatograph equipped with a nitrogen-selective detector, for trazodone quantitation.

Kinetics of fenfluramine isomers in the rat.

The kinetics of fenfluramine isomers were studied in the rat following oral doses of racemic fenfluramine. The data, analyzed using an analogue computer, indicate that the d-fenfluramine is metabolised and excreted at a slower rate than the 1-isomer, resulting in higher plasma and brain concentrations. The kinetic parameters of both isomers were dose-dependent.

Studies on some pharmacological activities of 7-nitro-2-amino-5-phenyl-3H-1,5-benzodiazepine (CP 1414 S) in the rat. A comparison with diazepam.

Brain distribution and various pharmacological effects of 7-nitro-2-amino-5-phenyl-1,5-benzodiazepine (CP 1414 S) and diazepam were studied in rats. Injected at 10 mg/kg i.p.

Effects of chronic treatment with di-(2-ethylhexyl) phthalate on rat liver microsomal activities.

The effects of chronic di-(2-ethylhexyl)phthalate (DEHP) on liver microsomal activity were studied in rats. Daily doses of 50 and 500 mg/kg for 4 weeks did not affect O-demethylation, aromatic hydroxylation, N-demethylation, C3-hydroxylation, styrene monooxygenase, glutamic-oxalacetic and glutamic-pyruvic transaminases (GOT, GPT). Inhibition of glutathione-S-transferase A and C and induction of epoxide hydrase, glutathione-S-transferase B and nitroreductase activity were instead observed.