Inhibitory effects of carvone isomers on the GABAA receptor in primary cultures of rat cortical neurons

MARIELA SÁNCHEZ-BORZONE; LETICIA DELGADO MARÍN; DANIEL A. GARCÍA

CHIRALITY

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: New York; Año: 2014 vol. 26 p. 368 - 372

0899-0042

Carvone is a natural terpene which can be purified as R-(-) or S-(+) enantiomers. There are many reports about its antibacterial, antifungal and insecticide activities, and also of some effects on the nervous system, where both enantiomers showed different potencies. Considering that the GABAA receptor is a major insecticide target, we studied the pharmacological activity of both carvone enantiomers, and of thujone as a reference compound acting on the receptor, on native GABAA by determining their effects on benzodiazepine recognition sites using primary neuronal cultures. Both isomers were able to inhibit the GABA-induced stimulation of [3H]flunitrazepam binding, suggesting their interaction with the GABAA receptor as negative allosteric modulators. Their activity was comparable to that described for thujone in the present article, with the R-(-)-carvone being the more similar and potent stereoisomer. The different configuration of the isopropenyl group in position 5 thus seems to be significant for receptor interaction and the bicycle structure not to be critical for receptor recognition. The concentrations necessary to induce negative modulation of the receptor were not cytotoxic in a murine neuron culture system. These results would confirm that, at least partially, the reported insecticide activity of carvones may be explained by their interaction with the GABAA receptor at its non-competitive blocker site. Page 3 of 18 John Wiley & Sons Chirality