BEHAVIORAL-STUDIES ON LEK-8804, A NEW ERGOLINE DERIVATIVE WITH POTENT5-HT1A RECEPTOR AGONIST AND 5-HT2 RECEPTOR ANTAGONIST ACTIVITY

The 5-HT1A receptor-mediated tail flick response in rats and the 5-HT2 receptor-mediated head twitch response in mice were used to study the functional activity of a new ergoline derivative, 9,10-didehydro-N-(2 -propynyl)-6-methylergoline-8 beta-carboxamide (LEK-8804). LEK-8804 do se-dependently elicited spontaneous tail flicks in rats, indicating a full 5-hydroxytryptamine(1A). (5-HT1A) agonist activity. This effect w as very similar to that produced by the selective 5-HT1A agonist 8-OH- DPAT, both in terms of potency and time-effect relationship, and was b locked by the selective 5-HT1A antagonist NAN-190. In contrast, LEK-88 04 by itself failed to produce head twitches in mice but dose-dependen tly inhibited the 5-hydroxytryptophan(5-HTP)-induced behavior. The inh ibitory effect of LEK-8804 upon 5-HTP-induced head twitches was not at tenuated by the selective 5-HT1A,, antagonist NAN-190. This indicates that probably not the agonist action on 5-HT1A receptors but instead t he antagonism on 5-HT2, receptors was involved in the inhibition of he ad twitch response. It is suggested that LEK-8804 is a potent full 5-H T1A, receptor agonist with possible 5-HT2 receptor antagonist properti es.