V. Hadrava et al., PARTIAL AGONISTIC ACTIVITY OF R-ENANTIOMERS AND S-ENANTIOMERS OF 8-OH-DPAT AT 5-HT1A RECEPTORS, Journal of psychiatry & neuroscience, 21(2), 1996, pp. 101-108
In this study, the 5-HT1A agonistic activity of R- and S-enantiomers o
f the prototypical 5-HT1A agonist 8-OH-DPAT was investigated using in
vivo microiontophoresis and the hypothermic response in rats. Both the
R- and S-enantiomers suppressed current-dependently the firing activi
ty of dorsal hippocampus CA(3) pyramidal neurons, The number of spikes
suppressed/nA of R-(+)-OH-DPAT was about 2-fold greater than that of
S-(-)-OH-DPAT, which indicates greater agonistic activity of the R-ena
ntiomer. The determination of the effectiveness of 5-HT in suppressing
the firing activity of CA(3) pyramidal neurons prior to and during ap
plication of either the R- or S-enantiomer showed that both compounds
antagonized the effect of 5-HT, thus demonstrating their partial agoni
stic activity, Racemic 8-OH-DPAT produced a dose-dependent hypothermia
which was attenuated by the 5-HT1A antagonist pindolol, but not by th
e nonselective 5-HT antagonist methysergide. Similarly, both R- and S-
enantiomers induced a dose-dependent hypothermia, which was greater an
d longer lasting in the case of R-(+)-OH-DPAT when compared to S-(-)-O
H-DPAT. In conclusion, R-(+)-OH-DPAT displayed a greater agonistic act
ivity at 5-HT1A receptors than S-(-)-OH-DPAT, both in suppressing firi
ng activity of CA(3) pyramidal neurons and in decreasing body temperat
ure, Nevertheless, both compounds behaved as partial agonists.