The heritability of antinociception II: pharmacogenetic mediation of three over-the-counter analgesics in XXXX .

@entity19 @entity117 @entity376 @entity74 @entity1286 @entity3352 @entity1443 @entity1543 @entity7840
Chromosomal loci containing genes affecting antinociceptive sensitivity to @entity1286 have been identified, but virtually nothing is known about the genetic mediation of sensitivity to over-the-counter analgesics. Such knowledge would be of great clinical interest, as prodigious interindividual variability has been noted in the efficacy of these ubiquitously used drugs. In the present study, we assessed heritability and genetic correlations among three over-the-counter analgesics in @entity19 of 12 inbred @entity19 strains on the 0.9% @entity1543 (i.p.) writhing test. Analgesics included the centrally acting analgesic, @entity1443 (150 mg/kg, s.c.), and the nonsteroidal anti-inflammatory drugs (NSAIDs), @entity3352 (40 mg/kg, s.c.) and @entity376 - @entity117 (800 mg/kg, s.c.). Significant strain differences in sensitivity to each of the drugs were observed, with narrow-sense heritability estimates ranging from 23 to 45%. Similar strains were sensitive and resistant, respectively, to the two NSAIDs (r(s) = 0.64). In contrast, a completely different pattern of sensitivities was observed for @entity1443 , implying @entity74 (r(s) = 0.29 and 0.02) compared with the NSAIDs. Additional experiments were performed on two strains, C57BL/6 and @entity7840 /2, with extreme sensitivities to @entity1443 . Plasma @entity1443 levels in these strains were not significantly different during the time of antinociception assessment, suggesting the existence of genetic factors affecting @entity1443 pharmacodynamics rather than pharmacokinetics.
