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Dopamine receptor binding of a novel dibenzodioxazocine derivative, EGYT-2509.
Dopamine receptor binding of a novel dibenzodioxazocine derivative, EGYT-2509.
- Source :
-
Polish journal of pharmacology and pharmacy [Pol J Pharmacol Pharm] 1985 May-Jun; Vol. 37 (3), pp. 253-61. - Publication Year :
- 1985
-
Abstract
- The binding of novel dibenzodioxazocine derivatives to rat striatal dopamine receptors was studied in vitro, using 3H-spiperone as radioligand. The biochemical-pharmacological characteristics of the effect of a selected representative, EGYT-2509 are discussed in details. The parameters of specific spiperone binding to rat striatal membrane preparation (KD = 0.550 nM, Bmax = 465 fmole/mg protein) as well as the displacing potencies of known dopamine receptor ligands matched closely the corresponding values in the literature. Using 0.4 nM radioligand, a Ki value of 404 nM was obtained for EGYT-2509; the binding of the drug had a minor serotonergic component. EGYT-2509 behaved as a dopamine receptor antagonist in all functional in vitro biochemical-pharmacological tests (striatal adenylate cyclase, striatal dopamine release, prolactin release from pituitary) performed previously. The drug exhibited a marked preference for adenylate cyclase-coupled (D1) dopamine receptors, followed by the 3H-spiperone displacing potency at striatal receptors. It was a rather weak antagonist both at striatal dopamine autoreceptors and at the receptors controlling prolactin release. Finally, when comparing the structure-activity relationships obtained with dibenzo-dioxazocines in the dopamine receptor binding assay with the relative pharmacological potencies of a structurally related neuroleptic group, i.e. of phenothiazines, a definite parallelism could be demonstrated.
- Subjects :
- Adenylyl Cyclases metabolism
Animals
Antipsychotic Agents metabolism
Binding, Competitive
Corpus Striatum metabolism
Dibenzoxazepines pharmacology
Female
In Vitro Techniques
Kinetics
Male
Motor Activity drug effects
Radioligand Assay
Rats
Spiperone metabolism
Dibenzoxazepines metabolism
Receptors, Dopamine metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0301-0244
- Volume :
- 37
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Polish journal of pharmacology and pharmacy
- Publication Type :
- Academic Journal
- Accession number :
- 2866498