biostudies-literatureUnknown14Harman T<b>Background:</b> T-type Ca²⁺ channels (Ca_v3) represent emerging therapeutic targets for a range of neurological disorders, including epilepsy and pain. To aid the development and optimisation of new therapeutics, there is a need to identify novel chemical entities which act at these ion channels. A number of synthetic cannabinoid receptor agonists (SCRAs) have been found to exhibit activity at T-type channels, suggesting that cannabinoids may provide convenient chemical scaffolds on which to design novel Ca_v3 inhibitors. However, activity at cannabinoid type 1 (CB₁) receptors can be problematic because of central and peripheral toxicities associated with potent SCRAs. The putative SCRA MEPIRAPIM and its analogues were recently identified as Ca<Frontiers in physiology1086243https://www.ebi.ac.uk/biostudies/studies/S-EPMC10110893biostudies-literatureMEPIRAPIM-derived synthetic cannabinoids inhibit T-type calcium channels with divergent effects on seizures in rodent models of epilepsy.PMC10110893Howland JGSnutch TPAmetovski ABanister SDGreba QHarman TArnold JCKevin RCUdoh MMcElroy DLAnderson LLDoohan PTMarkham JBladen CMcGregor ISLaprairie RBfalseMEPIRAPIM-derived synthetic cannabinoids inhibit T-type calcium channels with divergent effects on seizures in rodent models of epilepsy.<b>Background:</b> T-type Ca²⁺ channels (Ca_v3) represent emerging therapeutic targets for a range of neurological disorders, including epilepsy and pain. To aid the development and optimisation of new therapeutics, there is a need to identify novel chemical entities which act at these ion channels. A number of synthetic cannabinoid receptor agonists (SCRAs) have been found to exhibit activity at T-type channels, suggesting that cannabinoids may provide convenient chemical scaffolds on which to design novel Ca_v3 inhibitors. However, activity at cannabinoid type 1 (CB₁) receptors can be problematic because of central and peripheral toxicities associated with potent SCRAs. The putative SCRA MEPIRAPIM and its analogues were recently identified as Ca<2023-01-01T00:00:00Z20232026-05-28T17:58:51.603Z2024-12-03T15:59:54.595ZS-EPMC101108933708224110.3389/fphys.2023.1086243