Pharmacology of Cav1 (L-Type) Channels

Drug Targets in the Voltage-Gated Calcium Channel Family: Why Some Are and Some Are Not

“…Indeed, the firstgeneration Ca 21 channel blockers were essentially "accidental" discoveries (although it is clear, however, that these drugs have proved subsequently to be invaluable molecular tools with which to dissect and analyze channel function). 1,5,14,15,169,171,172,179 Second, the drugs were discovered in biological assay systems with a direct and readily observable relationship between the measured response in vitro and in vivo-vascular smooth muscle tension and blood pressure-and the desired therapeutic goal of antianginal and antihypertensive activity. Third, the cardiovascular system is dominated by the activity of the Ca V l class of channel; hence, differential functional contributions by other classes of channel are relatively unimportant, and fine-tuning of drug action occurs essentially within one channel class.…”

“…However, the L-type Ca 21 channel is also recognized by a wide variety of other chemical structures both naturally occurring and synthetic, consistent with a general role for ion channels as multiple pharmacological receptors. 4,5,12 Voltage-gated Ca 21 channels are members of a superfamily of ion channels that includes Na 1 , K 1 , and Ca 21 channels that share significant structural and functional homology. 13 There are several members of the Ca 21 channel subfamily that may be distinguished by their structure, subunit composition, location, function, and pharmacology ( Fig.…”

“…However, the control of Ca 21 mobilization and storage processes still represents an ongoing therapeutic possibility in a variety of cardiovascular, endocrine, and neuronal disorders. [1][2][3][4][5] The physiologic control of Ca 21 depends upon a specific set of cellular conditions:…”

Molecular Pharmacology of Non-L-type Calcium Channels

“…However, DHPs do not appear to discriminate among various Ca v 3 family members, and many examples in the literature showing DHP block of Ca v 3 currents [128,129,130,131] may be due to action on multiple Ca v 3 channel isoforms. In general, as demonstrated for Ca v 1 family members, DHPs interact with the domains III and IV S5-S6 regions [reviewed in 31,124, also see the review article by D. Triggle in this issue], as summarized in Fig. (1).…”

Selective inhibitory action of Biginelli-type dihydropyrimidines on depolarization-induced arterial smooth muscle contraction

“…The aim of our study was to describe the characteristics of four newly synthesized previously uncharacterized Biginelli type dihydropyrimidines, whose molecular conformation is in accordance with the Triggle dihydropyridine receptor binding model, [22] and to obtain novel pharmacological data regarding their activity and selectivity of action on depolarization versus noradrenaline‐induced vascular smooth muscle contraction in comparison with the reference calcium channel blocker nifedipine. Data we obtained on these novel compounds show that some exhibit a similar efficacy to that of the reference drug, with an even better selectivity for the inhibition of depolarization‐induced contraction.…”