Pharmacologic analysis of non-synonymous coding h5-HT2A SNPs reveals alterations in atypical antipsychotic and agonist efficacies.

The 5-HT(2A)-serotonin receptor is a major molecular target for most atypical antipsychotic drugs as well as most hallucinogens, which can exacerbate psychotic symptoms. In this study, we examined whether random sequence variations in the gene (single nucleotide polymorphisms, SNPs) encoding the 5-HT(2A)-serotonin receptor could explain inter-individual variability in atypical antipsychotic and agonist drug response. We examined the in vitro pharmacology of four non-synonymous SNPs, which give rise to T25N, I197V, A447V, and H452Y variant 5-HT(2A)-serotonin receptors. Our data indicate that these non-synonymous SNPs exert statistically significant, although modest, effects on the affinity and functional effects of several currently approved atypical antipsychotics (aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone). Also, the 5-HT(2A) receptor SNPs slightly altered the potency and relative efficacy of a small number of selected agonists (2,5-dimethoxy-4-iodoamphetamine, tryptamine, 5-hydroxytryptamine, m-chlorophenylpiperazine, and 5-methoxy-N, N-dimethyltryptamine). In all, our results show that the in vitro pharmacological effects of the SNPs are drug specific.

Comparison in the same environment of calving problems in heifers from herds with a history of a low and high incidence of dystocias.

The incidence of dystocias and the calving performance of primiparous Hereford heifers from 2 herds, one with a low (A) and the other a high (B) dystocia history, were compared when all animals were run on the same property in southern Queensland. The dystocia incidence was 21.4% for Herd A heifers and 40.5% for Herd B heifers (P approximately equal to 0.10). While Herd A heifers had significantly (P < 0.05) heavier calves than Herd B heifers (29.1 v 27.7 kg), the ratio of calf birth weight to dam pelvic brim area was 0.11 kg/cm2 for both groups. Differences in the size of the maternal pelvis, calf oversize and the type of presentation recorded for assisted births did not satisfactorily explain the difference in the incidence of dystocias. The circumstantial evidence indicated that inherent factors may affect dystocia.

A survey of dystocia in beef cattle in Southern Queensland.

Data relating to dystocia were obtained for 22% of beef herds in the Roma region of southern Queensland. In 1973 dystocia incidence in 23,129 maiden heifers was 12%; 4% of heifers and 7% of calves died. Thirty-five per cent of the 444 herds surveyed had more than a 10% incidence of dystocia, and 10% had more than a 30% incidence of dystocia. Only 6% of herds had no dystocia. Among the 73% of producers considering dystocia a problem in most years, 14% regarded it as a major problem. The incidence of dystocia in heifers was significantly higher in Poll Hereford than Hereford herds, which in turn were higher than other breeds of cattle. Poll Hereford and Hereford owners were the most concerned about dystocia but did not supervise calving more frequently. Dystocia and attitude were also examined in relation to degree of supervision at calving and size of the breeding herd.