Antinociceptive action of amlodipine blocking N-type Ca2+ channels at the primary afferent neurons in mice.
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Murakami M, Nakagawasai O, Fujii S, Kameyama K, Murakami S, Hozumi S, Esashi A, Taniguchi R, Yanagisawa T, Tan-no K, Tadano T, Kitamura K, Kisara K
Antinociceptive action of amlodipine blocking N-type Ca2+ channels at the primary afferent neurons in mice.
Eur J Pharmacol. 2001 May 11;419(2-3):175-81.
- PubMed ID
- 11426839 [ View in PubMed]
- Abstract
We investigated the antinociceptive action of amlodipine, a dihydropyridine derivative, which acts on both L- and N-type voltage-dependent Ca2+ channels (VDCCs), in mice. Intrathecal injection of amlodipine (300 nmol/kg) significantly shortened the licking time in the late phase of a formalin test, while no effect was found with another dihydropyridine derivative, nicardipine (300 nmol/kg). Cilnidipine and omega-conotoxin GVIA also showed marked analgesic effects under the same experimental conditions. Transcripts of alpha1A, alpha1B, alpha1E, alpha1F, alpha1H, beta3, and beta4 subunits were detected by polymerase-chain reaction (PCR) in the dorsal root ganglion, suggesting the existence of a variety of voltage-dependent Ca2+ channels. Electrophysiological experiments showed that amlodipine and cilnidipine inhibit N-type currents in the dorsal root ganglion cells. These results suggest that amlodipine, cilnidipine, and omega-conotoxin GVIA exert their antinociceptive actions by blocking N-type Ca2+ channels in the primary nociceptive afferent fibers. Blocking of the Ca2+ channels results in attenuation of synaptic transmission of nociceptive neurons. Furthermore, it is suggested that some N-type Ca2+ channel blockers might have therapeutic potential as analgesics when applied directly into the subarachnoidal space.
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 Nilvadipine Voltage-dependent calcium channel subunit alpha-2/delta-3 Protein Humans UnknownInhibitorDetails