Preclinical pharmacology of FG5893: a potential anxiolytic drug with high affinity for both 5-HT1A and 5-HT2A receptors
| Autor: | Anders Björk, Thorsten Klint, Jan Svartengren, Gunnar Andersson, Agneta Albinsson |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Male
Agonist medicine.medical_specialty medicine.drug_class In Vitro Techniques Piperazines Body Temperature Rats Sprague-Dawley Radioligand Assay Internal medicine Avoidance Learning medicine Animals Pindolol Receptor Swimming 5-HT receptor Brain Chemistry Pharmacology 8-Hydroxy-2-(di-n-propylamino)tetralin Behavior Animal Depression Chemistry Nicotinic Acids Brain Biological activity Receptor antagonist Rats Endocrinology Anti-Anxiety Agents Mechanism of action Receptors Serotonin Serotonin Antagonists Vocalization Animal medicine.symptom Corticosterone medicine.drug Behavioural despair test |
| Zdroj: | European Journal of Pharmacology. 261:285-294 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/0014-2999(94)90119-8 |
| Popis: | The effects of FG5893 were evaluated by several different methods; rats were used as experimental animals. Receptor binding studies revealed that FG5893 (2-(4-(4,4-bis(4-fluorophenyl)butyl)-1-piperazinyl)-3-pyridinecarboxy lic acid methyl ester) binds with high affinity to both 5-HT1A (Ki = 0.7 nM) and 5-HT2A receptors (Ki = 4.0 nM) but has only low affinity for the 5-HT2C receptor (Ki = 170 nM). FG5893 dose dependently reduced body temperature, and this effect was inhibited by pretreatment with (+/-)-pindolol. FG5893 (0.1 mg/kg) significantly inhibited head twitch behaviour induced by DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) and FG5893 was also a potent inhibitor of ultrasound vocalization in rat pups (0.3 mg/kg) and of a passive avoidance response (0.1 mg/kg) in mature animals. FG5893 inhibited the cage-leaving response and induced part of the 5-HT behavioural syndrome, but only at very high doses (5 and 10 mg/kg, respectively). At increased doses (1 mg/kg), FG5893 also elicited corticosterone release and reduced the immobility time in the forced-swim test (1 mg/kg). Together, these data indicate that the mixed 5-HT1A receptor agonist/5-HT2A receptor antagonist FG5983 is a potent stimulator of presynaptic 5-HT1A receptors but is less active at the postsynaptic site. FG5893 had potent anxiolytic-like effects both on separation-induced ultrasound vocalization in rat pups and on a passive avoidance response. At increased doses, FG5893 possessed an antidepressant-like property. |
| Databáze: | OpenAIRE |
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