Stereo-selective activity of menthol on GABAA receptor.

CORVALAN N.; ZYGADLO J; GARCIA DA

CHIRALITY

John Wiley & Sons, Inc.

Año: 2009 vol. 21 p. 525 - 530

0899-0042

Menthol is a naturally occurring compound which has three chiral centres that define eight possible optically actives stereoisomers. It was previously reported neuroactivity of menthol and related agents by affecting neuronal intracellular signaling or by modulation of neurotransmitter-gated currents. Furthermore it was described the stereo-selectivity of menthol in its analgesic activity as well as in its sensory properties and other biological activities. The present study is the first contribution to the description of stereo-selectivity of GABAA receptor against the most of the possible isomers of menthol, discussed in terms of their chirality. The results showed that only (+)-menthol, among the five stereoisomers analyzed, was active, stimulating in a dose-response manner the binding of an allosteric GABAA receptor ligand. Taking into account these results, and comparing them with those of some active phenolic compounds, it is strongly suggested that the existence of a relative spatial location of its substituents with respect to the ring (equatorial position of all substituents and (1S,2R,5S)-configuration) as well as the presence in the cyclic molecule of an aliphatic  non polar group (isopropyl) with free rotation near to a polar group (hydroxyl) are crucial points to demonstrate activity on the receptor.