Isoquinoline Derivatives Isolated from the Fruit of Annona muricata as 5-HTergic 5-HT1A Receptor Agonists in Rats: Unexploited Antidepressive (Lead) Products
- 1 November 1997
- journal article
- Published by Oxford University Press (OUP) in Journal of Pharmacy and Pharmacology
- Vol. 49 (11), 1145-1149
- https://doi.org/10.1111/j.2042-7158.1997.tb06058.x
Abstract
The fruit and the leaves of Annona muricata (Annonaceae) are used in traditional medicine for their tranquillizing and sedative properties. Extracts of the plant have been shown to inhibit binding of [3H]rauwolscine to 5-HTergic 5-HT1A receptors in calf hippocampus, and three alkaloids, annonaine (1), nornuciferine (2) and asimilobine (3), isolated from the fruit have been shown to have IC50 values of 3 microM, 9 microM and 5 microM, respectively, although in ligand-binding studies it was not possible to determine whether interaction of these ligands with the receptor was agonistic or antagonistic. This paper presents the results of functional assays of the alkaloids. The inhibition of cAMP accumulation was tested in NIH-3T3 cells stably transfected with the 5-HT1A receptor from man. None of the alkaloids showed antagonistic properties towards the 5-HT1A receptors because in the antagonistic tests no influence on the forskolin-stimulated increase of cAMP level was detected. Full agonistic properties were measured for all three compounds; the inhibition constants (Ki) for 1, 2 and 3 were < 10 microM. Inhibition of the binding of the radioligand to the 5-HT1A receptor was observed in every ligand-binding assay performed with the alkaloids; the Ki values for 1, 2 and 3 were in the microM range. These results imply that the fruit of Annona muricata possesses anti-depressive effects, possibly induced by compounds 1, 2 and 3, and that in the past potent leads for the development of anti-depressive therapeutics have not been used.This publication has 11 references indexed in Scilit:
- Screening of medicinal plants from Suriname for 5-HT1A ligands: Bioactive isoquinoline alkaloids from the fruit of Annona muricataPhytomedicine, 1997
- Serotonin 5-HT2 Receptor, Dopamine D2 Receptor, and α1 Adrenoceptor Antagonists. Conformationally Flexible Analogues of the Atypical Antipsychotic SertindoleJournal of Medicinal Chemistry, 1996
- Newp-Quinonoid Aporphine Alkaloids and Antiplatelet Aggregation Constituents ofHernandia sonoraPlanta Medica, 1995
- Effects of Various Isoquinoline Alkaloids on In Vitro 3H-Dopamine Uptake by Rat Striatal SynaptosomesJournal of Natural Products, 1995
- Bioactive Constituents from the Flower Buds and Peduncles of Lindera megaphyllaJournal of Natural Products, 1995
- Current advances and trends in the treatment of depressionTrends in Pharmacological Sciences, 1994
- β-Carbolines and Tetrahydroisoquinolines: Detection and Function in MammalsPlanta Medica, 1991
- Motor inhibition induced by aporphine derivatives in the mouseJournal of Pharmacy and Pharmacology, 1983
- Inhibition of Butyrylcholinesterase Activity by Some Isoquinoline AlkaloidsPlanta Medica, 1983
- Inhibition of Acetylcholinesterase Activity by some Isoquinoline Alkaloids*,**Planta Medica, 1983