4-Oxospiro[benzopyran-2,4'-piperidines] as selective alpha 1a-adrenergic receptor antagonists.

The 4-oxospiro[benzopyran-2,4'-piperidine] ring system is contained within potent class III antiarrhythmic agents. We highlight how these agents can be chemically transformed into a new class of potent (< 1 nM) and selective (> 25-fold) alpha 1a-receptor subtype adrenergic antagonists.

Design and synthesis of N-alkylated saccharins as selective alpha-1a adrenergic receptor antagonists.

Benign prostatic hyperplasia can be managed pharmacologically with alpha-1 adrenergic receptor antagonists. Agents that demonstrate selectivity for the alpha-1a receptor subtype may offer advantages in clinical applications with respect to hypotensive side effects. The N-alkylated saccharins reported here represent a new class of subtype selective alpha-1a adrenergic receptor antagonists which demonstrate potent effects on prostate function in vivo and are devoid of blood pressure side effects.

Seasonal alteration in taste detection and recognition threshold in seasonal affective disorder: the proximate source of carbohydrate craving.

Increased appetite with associated carbohydrate craving are core symptoms of seasonal affective disorder (SAD) and have been attributed to decreased central serotonergic function. The proximate mechanisms for centrally mediated selective macronutrient consumption are unknown. We questioned whether seasonal alterations in taste sensation could serve as a mediator of dietary intake, as implied by the term 'craving'.

Distinct binding and cellular properties of synthetic (+)- and (-)-discodermolides.

Background: Cell permeable ligands of low molecular weight can be used to dissect complex cellular processes. During the past several years this approach has been particularly important in the study of intracellular signal transduction. Discodermolide, a marine natural product, appears to inhibit a signaling pathway in immune cells.