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Biomedical subjects

V H Sethy

Publications and source records attributed to V H Sethy.

At least 55 records · Page 3Linked to original sources
PubMed1986

The effect of proadifen on the metabolism of adinazolam.

Binding affinities of adinazolam and its metabolite mono-N-demethyladinazolam, U-42352, to the brain tissue are not altered by the presence of proadifen (SKF-525A) in [3H]flunitrazepam [( 3H]FNZ) binding assays in-vitro. Pretreatment of mice with proadifen significantly blocked the ability of intravenously administered adinazolam to inhibit [3H]FNZ binding in the studies ex-vivo. The binding profile of [3H]FNZ to the brain tissue was not significantly different when animals were treated with U-42352 or proadifen with U-42352. These results suggest that proadifen may block the conversion of adinazolam to its active metabolite U-42352.

Animals↗
PubMed1986

Rapid changes in central beta-adrenergic receptors after chronic intravenous infusion of antidepressants.

The effects of intravenous infusion of desipramine (1, 3, 10, and 60 mg/kg/24 hr), amitriptyline, zimelidine, iprindole (3, 10, 30, 60, and 100 mg/kg/24 hr each), imipramine (10, 30, and 100 mg/kg/24 hr), or U-48,753E (1, 3, 10, and 30 mg/kg/24 hr) on the density of central beta-adrenergic receptors were investigated in Sprague-Dawley rats. A comparative study with oral desipramine (3 mg/kg/24 hr) for 74 hrs was also carried out. Desipramine, amitriptyline, zimelidine, iprindole, imipramine, and U-48,753E reduced the density of beta-adrenergic receptors in the cerebral cortex, and the effect seems to be dose-dependent. In the oral study, desipramine failed to down-regulate beta-adrenergic receptors. These results indicate that down-regulation of beta-adrenergic receptors can be rapidly achieved by intravenous infusion of drugs.

Administration, Oral↗
PubMed1984

Determination of biological activity of adinazolam and its metabolites.

Adinazolam and its metabolites inhibit [3H]flunitrazepam binding in-vitro. The binding affinities of these compounds is significantly enhanced in the presence of 10-5 M muscimol, indicating that both adinazolam and its metabolites are benzodiazepine agonists. In-vivo metabolism of adinazolam results in the formation of active metabolites.

Animals↗
PubMed1983

Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine.

Adinazolam, which is a 1-dimethylaminomethyl triazolobenzodiazepine, is an effective anxiolytic agent as defined by suppression of stress-induced increases in plasma corticosteroids. Adinazolam is also an effective antagonist of pentylenetetrazole. The 1-dimethylaminoethyl triazolo analog, U-43,465F, was inactive in the stressed rat test and only weakly active against pentylenetetrazole. Adinazolam and U-43,465F have been previously shown to have antidepressant activity in classical screening tests. They have also been found to potentiate the effect of norepinephrine and this is consistent with the activity of the known antidepressants; U-43,465F was found to be equieffective to imipramine in this test. Adinazolam was also effective; however, the magnitude of the potentiation was not as great. The uptake of norepinephrine was only weakly affected by either compound. Potentiation or uptake of serotonin were not significantly-altered pharmacological factors. Receptor binding studies were negative except at the benzodiazepine receptor. Chronic treatment with adinazolam did not decrease the number of beta-adrenergic receptors in the cerebral cortex of the rat, in contrast to the positive effect of imipramine. The discovery of triazolobenzodiazepines with antidepressant activity is of special interest. These agents will hopefully have lower toxicity than the tricyclic antidepressants and thus possess a more favourable therapeutic index. This would be advantageous in the treatment of depression.

5-Hydroxytryptophan↗
PubMed1983

Biochemical, functional and behavioral evaluation of a series of novel antipsychotic-like agents.

Two ethyl phenylpiperazine substituted isochromans and a related benzoxepine were discovered to have antipsychotic-like properties in animal screening models. Further evaluation of these compounds disclosed that, like neuroleptics, they blocked dopamine-stimulated adenylate cyclase, displaced 3H-spiperone in vitro, altered dopamine synthesis, and decreased conditioned avoidance and intracranial self-stimulation behavior. In contrast to classical neuroleptics but like clozapine, these compounds did not block apomorphine or amphetamine-induced chewing stereotypy in rats, raise serum prolactin concentrations, or increase 3H-spiperone binding after chronic dosing. However, unlike clozapine, the compounds of this series did not displace 3H-spiperone in either of two in vivo paradigms nor did they alter striatal acetylcholine concentrations. Taken together these data suggest that these isochroman and benzoxepine analogs would most probably not cause neuroleptic extrapyramidal side effects or prolactin elevations clinically. However, due to their atypical nature, their antipsychotic potential can only be assessed with certainty by careful clinical studies.

Adenylyl Cyclase Inhibitors↗
PubMed1982

1-(alkylamino)isochromans: hypotensives with peripheral and central activities.

A series of 1-[1-(3,4-dimethoxy-1H-2-benzopyran-1-yl)alkyl]-4-arylpiperazines that shows hypotensive activity in the conscious rat has been investigated. Structure-activity relationships are described. A typical example that was investigated in greater detail is 1-[2-(3,4-dihydro-6,7-dimethoxy-1H-2-benzopyran-1-yl)ethyl]-4-(4-fluorophenyl)piperazine. This compound decreases sympathetic nerve activity recorded from the external carotid and splanchnic nerves of baroreceptor-denervated cats and, therefore, has a central component to its mechanism of action. It also blocks pressor effects of norepinephrine and phenylephrine and is thus an alpha-adrenergic antagonist. Binding data characterize this as alpha 1-adrenergic receptor blockade.

Adrenergic alpha-Antagonists↗
PubMed1982

Benzodiazepine receptor number after acute administration of alprazolam and diazepam.

Acute administration of alprazolam and diazepam (50 mg/kg i.p.) significantly increased benzodiazepine receptors in distilled water-washed rat brain membrane preparation. Similar effects were not observed when rat brain membranes were washed with phosphate-buffered saline. Results are discussed with respect to solubilization of benzodiazepine receptors in distilled water.

Alprazolam↗
PubMed1982

Role of beta-adrenergic receptors in the antidepressant activity of alprazolam.

Chronic intravenous infusion of reserpine significantly increased beta-adrenergic receptors (beta-AR) in the cerebra cortex of rats. This increase in beta-AR is partially blocked by chronic treatment with alprazolam. However, similar effects were not observed with diazepam. These results indicate that beta-AR may be involved in the antidepressant activity of alprazolam.

Alprazolam↗
PubMed1980

High affinity binding of [3H]ethylketocyclazocine to rat brain homogenate.

Ethylketocyclazocine (Ekc), a potent kappa-receptor agonist, binds to opiate receptor sites in rat brain tissue. The binding was saturable with respect to the concentration of [3H]Ekc. The dissociation constant of Ekc-receptor complex was 1.8 nM and the maximum number of binding sites in the whole brain was 9.6 pmol/g of tissue. Opiate agonists and antagonists have a high affinity for [3H]Ekc binding sites, but results of present investigations failed to differentiate opiates thought to be specific for the mu- and kappa-receptors.

Animals↗
PubMed1978

Is GABA involved in analgesia?

The effect of morphine and naloxone on gamma-aminobutyric acid (GABA) concentration in discrete areas of the rat brain has been studied. Neither morphine nor naloxone had a significant effect on regional steady-state concentrations of GABA. The results have been discussed with respect to the role of GABA in pain and analgesia.

Aminobutyrates↗