Abstract

Ethnopharmacological relevance The convolvulacea Argyreia nervosa (Burm. f.) is well known as an important medical plant in the traditional Ayurvedic system of medicine and it is used in numerous diseases (e.g. nervousness, bronchitis, tuberculosis, arthritis, and diabetes). Additionally, in the Indian state of Assam and in other regions Argyreia nervosa is part of the traditional tribal medicine (e.g. the Santali people, the Lodhas, and others). In the western hemisphere, Argyreia nervosa has been brought in attention as so called “legal high”. In this context, the seeds are used as source of the psychoactive ergotalkaloid lysergic acid amide (LSA), which is considered as the main active ingredient.

Aim of the study As the chemical structure of LSA is very similar to that of lysergic acid diethylamide (LSD), the seeds of Argyreia nervosa (Burm. f.) are often considered as natural substitute of LSD. In the present study, LSA and LSD have been compared concerning their potential pharmacological profiles based on the receptor binding affinities since our recent human study with four volunteers on p.o. application of Argyreia nervosa seeds has led to some ambiguous effects.

Material and methods In an initial step computer-aided in silico prediction models on receptor binding were employed to screen for serotonin, norepinephrine, dopamine, muscarine, and histamine receptor subtypes as potential targets for LSA. In addition, this screening was extended to accompany ergotalkaloids of Argyreia nervosa (Burm. f.). In a verification step, selected LSA screening results were confirmed by in vitro binding assays with some extensions to LSD.

Results In the in silico model LSA exhibited the highest affinity with a pK i of about 8.0 at α 1A , and α 1B . Clear affinity with pK i >7 was predicted for 5-HT 1A , 5-HT 1B , 5-HT 1D , 5-HT 6 , 5-HT 7 , and D 2 . From these receptors the 5-HT 1D subtype exhibited the highest pK i with 7.98 in the prediction model. From the other ergotalkaloids, agroclavine and festuclavine also seemed to be highly affine to the 5-HT 1D -receptor with pK i >8. In general, the ergotalkaloids of Argyreia nervosa seem to prefer serotonin and dopamine receptors (pK i >7). However, with exception of ergometrine/ergometrinine only for 5-HT 3A , and histamine H 2 and H 4 no affinities were predicted. Compared to LSD, LSA exhibited lower binding affinities in the in vitro binding assays for all tested receptor subtypes. However, with a pK i of 7.99, 7.56, and 7.21 a clear affinity for 5-HT 1A , 5-HT 2 , and α 2 could be demonstrated. For DA receptor subtypes and the α 1 -receptor the pK i ranged from 6.05 to 6.85.