Substituted Pyridines as Sodium Channel Blockers

Class 1: Sodium Channel Blockers – Antiarrhythmic Drugs

Sodium channel blockers are vasodilator as well as natriuretic and diuretic agents.

Amiloride (100-400 micrograms) injected intra-arterially into the dog forelimb perfused at constant flow produced a prompt but transient dose-dependent decrease in perfusion pressure. Intravenous injection lowered systemic arterial pressure, but effects were small and transient except in doses exceeding 10 mg. We tested 11 analogues of amiloride, 3 other diuretics, and a hypotensive imidazopyra...

Modular, efficient synthesis of asymmetrically substituted piperazine scaffolds as potent calcium channel blockers.

A novel approach to the synthesis of substituted piperazines and their investigation as N-type calcium channel blockers is presented. A common scaffold exhibiting high activity as N-type blockers is N-substituted piperazine. Using recently developed titanium and zirconium catalysts, we describe the efficient and modular synthesis of 2,5-asymmetrically disubstituted piperazines from simple amine...

Corneal Anesthesia With Site 1 Sodium Channel Blockers and Dexmedetomidine.

PURPOSE Amino-amide or amino-ester local anesthetics, which are currently used for topical ocular anesthesia, are short acting and may delay corneal healing with long-term use. In contrast, site 1 sodium channel blockers (S1SCBs) are potent local anesthetics with minimal adverse tissue reaction. In this study, we examined topical local anesthesia with two S1SCBs, tetrodotoxin (TTX) or saxitoxin...

Sodium channel blockers and axonal protection in neuroinflammatory disease.

Although demyelination is a cardinal feature of neuroinflammatory conditions such as Guillain–Barré syndrome (GBS) and multiple sclerosis, axonal degeneration also occurs in these disorders. Because loss of axons causes permanent, non-remitting loss of neurological function, there is substantial interest in protection of axons in these situations. Protection of axons within white matter and per...