Selectivities of dihydropyridine derivatives in blocking Ca(2+) channel subtypes expressed in Xenopus oocytes.
Article Details
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Furukawa T, Yamakawa T, Midera T, Sagawa T, Mori Y, Nukada T
Selectivities of dihydropyridine derivatives in blocking Ca(2+) channel subtypes expressed in Xenopus oocytes.
J Pharmacol Exp Ther. 1999 Nov;291(2):464-73.
- PubMed ID
- 10525060 [ View in PubMed]
- Abstract
Some dihydropyridines (DHPs), such as amlodipine and cilnidipine, have been shown to block not only L-type but also N-type Ca(2+) channels; therefore, DHPs are no longer considered as L-type-specific Ca(2+) channel blockers. However, selectivity of DHPs for Ca(2+) channel subtypes including N-, P/Q-, and R-types are poorly understood. To address this issue at the molecular level, blocking effects of 10 DHPs (nifedipine, nilvadipine, barnidipine, nimodipine, nitrendipine, amlodipine, nicardipine, benidipine, felodipine, and cilnidipine) on four subtypes of Ca(2+) channels (L-, N-, P/Q-, and R-types) were investigated in the Xenopus oocyte expression system with the use of the two-microelectrode voltage-clamp technique. L-type Ca(2+) channels expressed as alpha(1C)alpha(2)beta(1a) combination were profoundly blocked by all DHPs examined, whereas blocking actions of these DHPs on R-type (alpha(1E)alpha(2)beta(1a)) channels were equally weak. In contrast, 5 of the 10 DHPs (amlodipine, benidipine, cilnidipine, nicardipine, and barnidipine) significantly blocked N-type (alpha(1B)alpha(2)beta(1a)) and P/Q-type (alpha(1A)alpha(2)beta(1a)) Ca(2+) channels. These selectivities of DHPs in blocking Ca(2+) channel subtypes would provide useful pharmacological and clinical information on the mode of action of the drugs including side effects and adverse effects.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Amlodipine Voltage-dependent calcium channel subunit alpha-2/delta-3 Protein Humans UnknownInhibitorDetails Amlodipine Voltage-dependent L-type calcium channel subunit beta-1 Protein Humans UnknownInhibitorDetails Amlodipine Voltage-dependent N-type calcium channel subunit alpha-1B Protein Humans UnknownInhibitorDetails Felodipine Voltage-dependent calcium channel subunit alpha-2/delta-1 Protein Humans YesInhibitorDetails Felodipine Voltage-dependent L-type calcium channel subunit alpha-1C Protein Humans YesInhibitorDetails Felodipine Voltage-dependent L-type calcium channel subunit beta-2 Protein Humans YesInhibitorDetails Nilvadipine Voltage-dependent calcium channel subunit alpha-2/delta-3 Protein Humans UnknownInhibitorDetails