Effects of the C3-methylated derivatives of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on central 5-hydroxytryptamine receptors.

The effects of the four possible C3-methylated stereoisomers of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) ((-)-CM-11, (+)-CM-11, (-)-CM-12, (+)-CM-12) on brain 5-hydroxytryptamine (5-HT) receptor functions were studied in rats. (-)-CM-11 and (+)-CM-12 inhibited dose dependently in all brain parts the accumulation of 5-hydroxytryptophan following decarboxylase inhibition. Their antipodes were inactive. The disappearance of 5-HT induced by alpha-propyldopacetamide was retarded by (-)-CM-11 and (+)-CM-12. The biochemically active isomers produced a flat body posture and forepaw treading. The results indicate that (-)-CM-11 and (+)-CM-12 stimulate 5-HT receptors directly although not as potently as 8-OH-DPAT. The concentration of dopamine was lowered and that of homovanillic acid was elevated by (+)-CM-11 and by both enantiomers of CM-12 in the corpus striatum and in the limbic system of rats. The accumulation of DOPA following decarboxylase inhibition was not markedly changed by any of the compounds. Locomotor activity was enhanced by (+)-CM-11 but not by any of the other compounds, and the effect was haloperidol-resistant. (+)-CM-11 induced no asymmetry in rats in which the corpus striatum was inactivated on one side. Thus, none of the isomers of CM-11 or CM-12 appears to have any effect on the dopamine receptors.