Pharmacological profile of an essential oil derived from Melissa officinalis with anti-agitation properties: focus on ligand-gated channels

Abuhamdah, Sawsan, Huang, Liping, Elliott, Mark S.J, Howes, Melanie-Jayne R, Ballard, Clive, Holmes, Clive, Burns, Alistair, Perry, Elaine K, Francis, Paul T, Lees, George and Chazot, Paul L (2008) Pharmacological profile of an essential oil derived from Melissa officinalis with anti-agitation properties: focus on ligand-gated channels. Journal of Pharmacy and Pharmacology, 60 (3), 377-384. (doi:10.1211/jpp.60.3.0014).

Abstract

A dual radioligand binding and electrophysiological study, focusing on a range of ligand-gated ion channels, was performed with a chemically-validated essential oil derived from Melissa officinalis (MO), which has shown clinical benefit in treating agitation. MO inhibited binding of [S-35] t-butylbicyclophosphorothionate (TBPS) to the rat forebrain gamma-aminobutyric acid (GABA)A receptor channel (apparent IC50 0.040 +/- 0.001 mg mL(-1)), but had no effect on N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropianate (AMPA) or nicotinic acetylcholine receptors. Electrophysiological analyses with primary cultures of rat cortical neurons demonstrated that MO reversibly inhibited GABA-induced currents in a concentration-dependent manner (0.01-1 mg mL(-1)), whereas no inhibition of NMDA- or AMPA-induced currents was noted. Interestingly, MO elicited a significant dose-dependent reduction in both inhibitory and excitatory transmission, with a net depressant effect on neurotransmission (in contrast to the classical GABA(A) antagonist picrotoxinin which evoked profound epileptiform burst firing in these cells). The anti-agitation effects in patients and the depressant effects of MO in in-vitro we report in neural membranes are unlikely to reflect a sedative interaction with any of the ionotropic receptors examined here

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Contributors

Author: Clive Holmes

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