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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The effect of putative 5-HT1A receptor antagonists on 8-OH-DPAT-induced hypothermia in rats and mice.

The effects of three putative 5-HT1A receptor antagonists (NAN-190, BMY 7378 and WB 4101) were studied on the hypothermia induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). In order to control for the alpha 1-adrenoceptor antagonist activity of NAN-190 and WB 4101, the effects of prazosin were also examined. Both NAN-190 and WB 4101 lowered body temperature in the mouse. This effect appeared to be due to their alpha 1-adrenoceptor antagonist effects as prazosin had a similar profile. Neither NAN-190, WB 4101 nor prazosin antagonised the hypothermic effects of 8-OH-DPAT. BMY 7378 slightly lowered body temperature but to a lesser extent than 8-OH-DPAT and, in contrast to the other compounds studied, also prevented a fall in body temperature on injection of 8-OH-DPAT. In the rat there was much less interference from alpha 1-adrenoceptor antagonist activity as both NAN-190 and prazosin only slightly reduced body temperature. In this species, however, NAN-190 showed marked antagonist activity against 8-OH-DPAT hypothermia. This was not due to alpha 1-adrenoceptor antagonist activity as prazosin had no effect. In the rat, as in the mouse, BMY 7378 had a partial agonist profile, whereas WB 4101 behaved essentially as an agonist. These results suggest that NAN-190 is a pure antagonist of 8-OH-DPAT-induced hypothermia in rats and that BMY 7378 and WB 4101 are, respectively, a partial agonist and an agonist in this test.(ABSTRACT TRUNCATED AT 250 WORDS)[1]


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