title: Pharmacological profile of an essential oil derived from Melissa officinalis with anti-agitation properties: focus on ligand-gated channels.
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 [35S] 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.
authors.affiliation: Centre for Integrative Neuroscience, School of Biological and Biomedical Sciences, Science Park, South Road, Durham University, Durham, UK.
authors.forename: Sawsan
authors.initials: S
authors.lastname: Abuhamdah
authors.forename: Liping
authors.initials: L
authors.lastname: Huang
authors.forename: Mark S J
authors.initials: MS
authors.lastname: Elliott
authors.forename: Melanie-Jayne R
authors.initials: MJ
authors.lastname: Howes
authors.forename: Clive
authors.initials: C
authors.lastname: Ballard
authors.forename: Clive
authors.initials: C
authors.lastname: Holmes
authors.forename: Alistair
authors.initials: A
authors.lastname: Burns
authors.forename: Elaine K
authors.initials: EK
authors.lastname: Perry
authors.forename: Paul T
authors.initials: PT
authors.lastname: Francis
authors.forename: George
authors.initials: G
authors.lastname: Lees
authors.forename: Paul L
authors.initials: PL
authors.lastname: Chazot
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D015640:Ion Channel Gating; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D008024:Ligands; D008297:Male; D031334:Melissa / Q000737:chemistry*; D009822:Oils, Volatile / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D011595:Psychomotor Agitation / Q000188:drug therapy; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism
chemical_list: D007473:Ion Channels; D008024:Ligands; D009822:Oils, Volatile; D011963:Receptors, GABA-A