OBJECTIVE The primary objective of this study was to determine if there was an increased risk of myocardial infarction (MI) in a high-risk hypertensive diabetic managed care population receiving combination antihypertensive therapy including a dihydropyridine (DHP) calcium channel blocker (CCB). METHODS A retrospective, population-based, case-control study design was used to determine the ris...

The whole-cell patch-clamp technique was used to study voltage-dependent calcium currents in primary cultures of myotubes and in freshly dissociated skeletal muscle from normal and dysgenic mice. In addition to the transient, dihydropyridine (DHP)-insensitive calcium current previously described, a maintained DHP-sensitive calcium current was found in dysgenic skeletal muscle. This current, her...

The vasorelaxing properties of calcium antagonists have been well established in both experimental and clinical settings during the past three decades. Fleckenstein et al. (13) first postulated a blockade of calcium channels by verapamil, a calcium antagonist. The first therapeutically useful dihydropyridine (DHP), nifedipine, was synthesized by Bossert and Vater (9), and formed the basis for a...

Ca(2+) sparks are localized intracellular Ca(2+) events released through ryanodine receptors (RyRs) that control excitation-contraction coupling in heart and smooth muscle. Ca(2+) spark triggering depends on precise delivery of Ca(2+) ions through dihydropyridine (DHP)-sensitive Ca(2+) channels to RyRs of the sarcoplasmic reticulum (SR), a process requiring a very precise alignment of surface a...

Voltage-gated LTCCs (L-type Ca2+ channels) are established drug targets for the treatment of cardiovascular diseases. LTCCs are also expressed outside the cardiovascular system. In the brain, LTCCs control synaptic plasticity in neurons, and DHP (dihydropyridine) LTCC blockers such as nifedipine modulate brain function (such as fear memory extinction and depression-like behaviour). Voltage-sens...

MALIGNANT hyperthermia (MH) is a life-threatening anesthesia-related complication characterized by a hypermetabolic response of skeletal muscle which can be triggered by anesthetic drugs such as halothane and succinylcholine. Although some genes have been identified to be involved in MH (such as the ryanodine receptor gene [RYR1] and the dihydropyridine receptor [DHP] gene) the underlying molec...

Epilepsy is a chronic disorder of the brain affecting around 50 million people in the world. Up to 30% of epileptic patients do not respond to available drugs and medical therapies. In this paper, anticonvulsant screening of 10 synthesized new derivatives of 1, 4-dihydropyridine-3, 5-dicarboxamides was performed. Anticonvulsant activity was evaluated by intravenous and intraperitoneal pentylene...

The voltage dependent N-type Ca channel (NCC) distributed in the nerve ending of the central and peripheral nerves. NCC is considered as potential therapeutic target for several pathological disorders like neuropathic pain and stroke disease. For understanding mechanism of action at the atomic level crystal structure provide valuable inside but lack of crystal structure of ion channel lead sequ...

In human hypertrophic cardiomyopathy and hypertension associated ventricular hypertrophy, chronic use of calcium channel blockers results in a significant regression of hypertrophy. The main objective of this study was to test the hypothesis that modulation of calcium influx through the voltage-sensitive L-type Ca2+ channel directly affects myocardial hypertrophy. Agents that modified calcium i...

Several large population based or clinical trial studies have suggested that certain dihydropyridine (DHP) L-type calcium channel blockers (CCBs) used for the treatment of hypertension may confer protection against the development of Alzheimer’s disease (AD). However, other studies with drugs of the same class have shown no beneficial clinical effects. In order to determine whether certain DHPs...