title: Behavioral studies on LEK-8804, a new ergoline derivative with potent 5-HT1A receptor agonist and 5-HT2 receptor antagonist activity.
abstract: 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 dose-dependently elicited spontaneous tail flicks in rats, indicating a full 5-hydroxytryptamine1A (5-HT1A) agonist activity. This effect was 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 blocked by the selective 5-HT1A antagonist NAN-190. In contrast, LEK-8804 by itself failed to produce head twitches in mice but dose-dependently inhibited the 5-hydroxytryptophan (5-HTP)-induced behavior. The inhibitory effect of LEK-8804 upon 5-HTP-induced head twitches was not attenuated by the selective 5-HT1A antagonist NAN-190. This indicates that probably not the agonist action on 5-HT1A receptors but instead the antagonism on 5-HT2 receptors was involved in the inhibition of head twitch response. It is suggested that LEK-8804 is a potent full 5-HT1A receptor agonist with possible 5-HT2 receptor antagonist properties.
authors.affiliation: Department of Pharmacology, R & D, LEK Pharmaceutical and Chemical Company, Ljubljana, Slovenia.
authors.forename: I
authors.initials: I
authors.lastname: Krisch
authors.forename: B
authors.initials: B
authors.lastname: Bole-Vunduk
mesh_terms: D006916:5-Hydroxytryptophan / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006257:Head; D007700:Kinetics; D008238:Lysergic Acid Diethylamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051379:Mice; D009068:Movement / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: D010879:Piperazines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; C086497:LEK 8804; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D008238:Lysergic Acid Diethylamide; D006916:5-Hydroxytryptophan