Trends in Pharmacological Sciences
ReviewVoltage-Gated Ion Channels in the PNS: Novel Therapies for Neuropathic Pain?
Section snippets
Neuropathic Pain
As defined by the International Association for the Study of Paini [1], pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage; chronic pain is pain that persists beyond the normal tissue healing time (usually 3 months); neuropathic pain is pain caused by a lesion of, or damage to, the somatosensory nervous system (Figure 1A). Chronic pain greatly impairs an individual's quality of life, is widely prevalent, and has significant cost. In the USA
CaV Channels
Voltage-gated Ca2+ channels (CaV) are broadly classified into three closely related groups based on genes coding the obligatory pore-forming α subunit: CaV1, CaV2, and CaV3 18, 19 (Figure 2). Three genes comprise the CaV3 subfamily (Figure 2A), and these channels give rise to the low-voltage activated (LVA) ‘T’-type current. T-type Ca2+ currents are present in dorsal root ganglia (DRG) neurons 20, 21, 22, 23, the basis of which is CaV3.2 and CaV3.3, at least in small- and medium-sized sensory
Concluding Remarks
It is evident that the data from preclinical animal models offers, in many instances, compelling arguments for a particular molecular pathway as being of fundamental importance to the development, maintenance, and therapeutic target value in neuropathic pain. Based on those results, human clinical trials are designed, subjects enrolled, data collated and subjected to multivariate analysis, and report, all too frequently, no significant effect [199]; the results with the CaV3.2 blocker ABT-639
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An anchor-tether ‘hindered’ HCN1 inhibitor is antihyperalgesic in a rat spared nerve injury neuropathic pain model
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2023, Journal of PainDiscovery of pimozide derivatives as novel T-type calcium channel inhibitors with little binding affinity to dopamine D<inf>2</inf> receptors for treatment of somatic and visceral pain
2022, European Journal of Medicinal ChemistryCitation Excerpt :Similar T1/2 value, 2.42 h ± 0.137, for compound 3s was obtained by pharmacokinetic analysis in mice (Fig. 10). Accumulating evidence suggests that Cav3.2 and/or Cav3.1 T-channels are promising targets for the development of novel medicines to treat intractable somatic and visceral pain [1,5–14], and also itch [19,20]. In the present study, we focused on pimozide, an antipsychotic agent with potent T-channel inhibitory activity [38], and conducted structural modifications of it to develop its derivatives with reduced affinity to dopamine D2 receptors and an unaltered or enhanced inhibitory effect against T-channels.