I. Krisch et B. Bolevunduk, BEHAVIORAL-STUDIES ON LEK-8804, A NEW ERGOLINE DERIVATIVE WITH POTENT5-HT1A RECEPTOR AGONIST AND 5-HT2 RECEPTOR ANTAGONIST ACTIVITY, Pharmacology, biochemistry and behavior, 47(2), 1994, pp. 301-305
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.