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.

1 The influence of the nitric oxide (NO) biosynthesis inhibitor N0-nitro-L-arginine methyl ester (L-NAME) on the gastric relaxation induced by peripheral vagal stimulation was investigated in the anaesthetized rat.2 Peripheral vagal stimulation (10 Hz, 10 V, 1 ms for 20 s) induced a reproducible biphasic response: a short-lasting increase followed by a more pronounced decrease in intragastric pressure. This response also occurred in reserpinized animals (5mg kg-, i.p., 24 h before the experiment) while atropine (1 mg kg1, i.v.) abolished the initial increase in intragastric pressure. 3 L-NAME (1-30mg kg-',i.v.) induced an increase in arterial blood pressure. L-NAME (1 mg kg-i.v.) had no influence on the vagally induced gastric response while L-NAME (10 and 30mgkg-' i.v.) significantly changed it: the initial increase in intragastric pressure was enhanced while the decrease in intragastric pressure was reduced or abolished. N0-nitro-L-arginine (L-NNA, l0 mg kg-%, i.v.) had the same effect.4 An i.v. infusion of phenylephrine (10pgkg-lmin-1) inducing a pressor response similar to that produced by L-NAME (30mgkg-1, i.v.) did not influence the vagal gastric response. Infusion of L-arginine (300mgkg-' bolus, then lOOmgkg-lh-') starting 30min beforehand, reduced the pressor effect and prevented the influence of L-NAME (lOmgkg-, i.v.) on the vagal gastric response. After injection of both atropine (lmgkg-', i.v.) and L-NAME (30mgkg-', i.v.), the vagally induced decrease in intragastric pressure was similar to that obtained under control conditions. 5 These results are consistent with NO being released and inducing gastric relaxation during peripheral vagal stimulation. In addition to NO, another inhibitory non-adrenergic non-cholinergic neurotransmitter is released.

In traditional medicine Gossypium barbadense L. is used against hypertension. Looking for a scientific basis for this use, the blood-pressure-lowering effect of the decoction of the leaves was confirmed. Fraction II (frII) of the crude extract of G. barbadense showed a dose-dependent hypotensive effect in anaesthetized rats. In hexamethonium-treated rats, the blood-pressure-lowering effect of frII was almost abolished. A small decrease of the blood-pressure-lowering effect was followed by an increase in the blood pressure. Phentolamine antagonized the increase in blood pressure in hexamethoniumtreated rats. High doses of atropine (4 mg/rat) suppressed both depressor and heart effects. In-vitro experiments revealed that atropine did not antagonize the contraction of the ileum of the rat. Tripelennamine in a concentration of 100 microg could not influence the contraction either, whereas 300 microg did. In the guinea-pig ileum 10 microg tripelennamine did not reduce the contraction significantly. In the mechanism of action of frII, acetylcholine receptors could be involved, but not histaminergic or adrenergic receptors. Although it is still not known which compound(s) in G. barbadense is (are) the active substance(s), the results obtained may explain the use of this plant in traditional medicine in Suriname.

The S. lycocarpum preparation may be useful against leishmaniasis and may have a good safety index, warranting further investigations into its active constituents and mechanism(s) of action.

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