Quipazine-metoclopramide inhibition of CB-154-induced prolactin suppression in rats: neurotransmitter-metabolite correlations.

The ability of quipazine and metoclopramide to protect rats from CB-154-induced suppression of serum prolactin concentrations was studied. These drugs affect whole brain concentrations of dopamine and serotonin, and their major metabolites dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid. Serum prolactin concentrations have been correlated with the concentrations of the neurotransmitters and their respective metabolites. Differences in the metabolite/precursor ratios have been used to compare turnover rates of the neurotransmitters dopamine and serotonin. Increased turnover of dopamine and decreased turnover of serotonin correlate with elevated prolactin concentrations for quipazine and metoclopramide administered together. The combination of quipazine and metoclopramide protects rats against CB-154-induced prolactin suppression better than either of the drugs given alone. This study suggests that a quipazine-metoclopramide regimen may have therapeutic potential for combating ergotlike fescue and other similar toxicities observed in cattle grazing on endophyte-infected pasture grasses.