Biomedical subjects

A A Kergaye

Publications and source records attributed to A A Kergaye.

3 recordsLinked to original sources

PubMed1994

Piperidinyltetralin sigma ligands.

Sigma receptor ligands have been proposed to be potential antipsychotic drugs based on their activity profile in animal behavioral models and their indirect modulation of dopaminergic function. Compound 15 (DuP 734) is a combined antagonist of sigma-1 and serotonin 5HT2 receptors, which has been entered into phase I clinical trials as a potential antipsychotic drug. Tetralins 1 and 2 were prepared to determine whether restriction of the conformation of 15 and its analogs may lead to differences in binding selectivity or in vivo profile. The syntheses and the structure-activity relationships of these compounds are reported herein. A reduced derivative, 14, had high affinity for sigma-1 and serotonin 5HT2 receptors as well as excellent oral activity in some animal antipsychotic models. Furthermore, compound 14 failed to cause catalepsy in the rat up to 90 mg/kg (po).

Aggression↗

PubMed1993

3-Substituted, 3-(4-pyridinylmethyl)-1,3-dihydro-1-phenyl-2H-indol-2-ones as acetylcholine release enhancers: synthesis and SAR.

A series of 3-substituted, 3-(4-pyridinylmethyl)-1,3-dihydro-1-phenyl-2H-indol-2-ones was synthesized and found to enhance the stimulus-induced release of neurotransmitter acetylcholine (AcCh), and by doing so, might be useful in treating cognitive disorders where the level of this neurotransmitter may be diminished in the brain, as in Alzheimer's disease. An attempt has been made to correlate the structure of the 3-substitution with the ability of the compounds to enhance the release of AcCh from the striatum region of rat brain preparations.

Acetylcholine↗

PubMed1992

Novel piperidine sigma receptor ligands as potential antipsychotic drugs.

sigma receptor ligands represent a new class of potential antipsychotic drugs. This paper presents the structure-activity relationships leading to novel disubstituted piperidine sigma ligands, which have little or no affinity for dopamine D2 receptors. Selectivity for sigma sites over dopamine D2 or serotonin 5-HT2 receptors appears to be governed by the chemical nature of the piperidine nitrogen substituent, its distance from the basic nitrogen, and its orientation relative to the other piperidine substituent. Several of these compounds have good oral potency in some animal models used to evaluate potential antipsychotic drugs. The N-cyclopropylmethyl ketones and ethers (e.g. 6i (DuP 734), 6q, 18a, and 18n) have the best in vivo potency. Compounds 6i (DuP 734) and 6q did not cause catalepsy in the rat, even at very high doses. On the basis of the pharmacology profiles of these sigma ligands, we propose these compounds may be effective antipsychotic drugs, which do not induce extrapyramidal side effects or tardive dyskinesia.

Animals↗