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Behavioral studies on LEK-8804, a new ergoline derivative with potent 5-HT1A receptor agonist and 5-HT2 receptor antagonist activity. 1994

I Krisch, and B Bole-Vunduk
Department of Pharmacology, R & D, LEK Pharmaceutical and Chemical Company, Ljubljana, Slovenia.

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.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008238 Lysergic Acid Diethylamide Semisynthetic derivative of ergot (Claviceps purpurea). It has complex effects on serotonergic systems including antagonism at some peripheral serotonin receptors, both agonist and antagonist actions at central nervous system serotonin receptors, and possibly effects on serotonin turnover. It is a potent hallucinogen, but the mechanisms of that effect are not well understood. LSD,Lysergide,LSD-25,Lysergic Acid Diethylamide Tartrate,Acid Diethylamide, Lysergic,Diethylamide, Lysergic Acid,LSD 25
D008297 Male Males
D009068 Movement The act, process, or result of passing from one place or position to another. It differs from LOCOMOTION in that locomotion is restricted to the passing of the whole body from one place to another, while movement encompasses both locomotion but also a change of the position of the whole body or any of its parts. Movement may be used with reference to humans, vertebrate and invertebrate animals, and microorganisms. Differentiate also from MOTOR ACTIVITY, movement associated with behavior. Movements
D010879 Piperazines Compounds that are derived from PIPERAZINE.
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006257 Head The upper part of the human body, or the front or upper part of the body of an animal, typically separated from the rest of the body by a neck, and containing the brain, mouth, and sense organs. Heads
D006916 5-Hydroxytryptophan The immediate precursor in the biosynthesis of SEROTONIN from tryptophan. It is used as an antiepileptic and antidepressant. 5-HTP,Hydroxytryptophan,Oxitriptan,Oxytryptophan,Tryptophan, 5-Hydroxy-,5 Hydroxytryptophan,5-Hydroxy- Tryptophan,Tryptophan, 5 Hydroxy
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001522 Behavior, Animal The observable response an animal makes to any situation. Autotomy Animal,Animal Behavior,Animal Behaviors

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