Inhibition of N-type calcium ion channels by tricyclic antidepressants – experimental and theoretical justification for their use for neuropathic pain
Fernanda C. Cardoso, Matthieu Schmit, Michael J. Kuiper, Richard J. Lewis, Kellie L. Tuck, Peter J. Duggan
Abstract
2.2 channels by TCAs. Two closely related binding modes, that occur in the channel cavity that exists between the selectivity filter and the internal gate, were identified. The TCAs are predicted to position themselves such that their ammonium side chains interfere with the selectivity filter, with some, such as amitriptyline, also appearing to hinder the channel's ability to open. This study provides the most comprehensive evidence to date that supports the notion that the blockade of neuronal calcium ion channels by TCAs is at least partially responsible for their analgesic effect.
Topics & Concepts
Neuropathic painTricyclicAnalgesicChemistryCalcium channelIon channelLigand-gated ion channelN-type calcium channelT-type calcium channelPharmacologyVoltage-dependent calcium channelBiophysicsCalciumReceptorStereochemistryMedicineBiologyBiochemistryOrganic chemistryIon channel regulation and functionPain Mechanisms and TreatmentsNeuroscience and Neuropharmacology Research