title: Comparison of the effects of a series of kappa-opioid receptor agonists upon sodium channel function in rat brain miniprisms.
abstract: The blockade of veratrine-stimulated phosphoinositide breakdown in rat cerebral cortical miniprisms has been used as a model of drug action on voltage-dependent sodium channels. The kappa-opioid agonists bremazocine, (+/-)- and (+)-trans-U-50488, U-62066 (spiradoline) and U-69593 inhibited the response to veratrine with IC50 values of 35, 13, 15, 9, and > 100 microM, respectively. Bremazocine, at concentrations inhibiting the response to veratrine, did not inhibit the phosphoinositide breakdown response to the sodium ionophore monensin, indicating the specificity of the assay for sodium channels. The inhibitory actions of bremazocine upon veratrine-stimulated phosphoinositide breakdown were not antagonised by naloxone. This study thus confirms previous data suggesting that the kappa-opioid receptor agonists can affect Na(+)-channel function in a manner unrelated to their actions at kappa-opioid receptors. However, for the compounds tested, such effects are only found at rather high concentrations of the compounds.
authors.affiliation: Department of Pharmacology, Umeå University, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Tiger
authors.forename: C J
authors.initials: CJ
authors.lastname: Fowler
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D044482:Benzeneacetamides; D001575:Benzomorphans / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D007295:Inositol Phosphates / Q000378:metabolism; D009270:Naloxone / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology
chemical_list: D000700:Analgesics; D044482:Benzeneacetamides; D001575:Benzomorphans; D007295:Inositol Phosphates; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D015222:Sodium Channels; D009270:Naloxone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C027248:bremazocine; C045444:U 69593; C051272:spiradoline