Benzodiazepines produce contrasting effects on the active membrane properties of an invertebrate neuron. 1985

K S Tan, and R D Sewell, and S H Roth

A perturbation of excitable membranes mediated by non-receptor (non-specific) mechanisms might be predicted from the hydrophobic nature of 1,4-benzodiazepines. Since correlations between membrane properties and neuronal effects have not been described for benzodiazepines, the effects of flurazepam, oxazepam and the benzodiazepine antagonist flumazepil (Ro 15-1788) were examined on both passive and active electrical properties of the membrane and neuronal discharge frequency. In this study, the isolated sensory neuron of the crayfish has been utilized as a neuronal model system. Flurazepam and flumazepil both enhanced the discharge frequency, in contrast to the depression produced by oxazepam. Discharge frequency was directly correlated with the maximum rate of rise of membrane potential during the threshold phase and was inversely correlated with spike threshold. In addition, the discharge frequency appeared to exhibit little dependence on peak amplitude, duration and the maximum rate of depolarization of the action potential. These findings are discussed in relation to non-specific mechanism(s) of action for benzodiazepines. It is suggested that, in the absence of a specific drug-receptor interaction, benzodiazepines in larger concentrations (greater than or equal to 50 mumol/l) exhibit selective membrane perturbations.

UI MeSH Term Description Entries
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D009475 Neurons, Afferent Neurons which conduct NERVE IMPULSES to the CENTRAL NERVOUS SYSTEM. Afferent Neurons,Afferent Neuron,Neuron, Afferent
D010076 Oxazepam A benzodiazepine used in the treatment of anxiety, alcohol withdrawal, and insomnia. Adumbran,Serax,Tazepam
D003400 Astacoidea A superfamily of various freshwater CRUSTACEA, in the infraorder Astacidea, comprising the crayfish. Common genera include Astacus and Procambarus. Crayfish resemble lobsters, but are usually much smaller. Astacus,Crayfish,Procambarus,Astacoideas,Crayfishs
D004553 Electric Conductivity The ability of a substrate to allow the passage of ELECTRONS. Electrical Conductivity,Conductivity, Electric,Conductivity, Electrical
D005442 Flumazenil A potent benzodiazepine receptor antagonist. Since it reverses the sedative and other actions of benzodiazepines, it has been suggested as an antidote to benzodiazepine overdoses. Flumazepil,Anexate,Lanexat,Ro 15-1788,Romazicon,Ro 15 1788,Ro 151788
D005479 Flurazepam A benzodiazepine derivative used mainly as a hypnotic. Apo-Flurazepam,Dalmadorm,Dalmane,Dormodor,Flurazepam Dihydrochloride,Flurazepam Hydrochloride,Flurazepam Mono-Perchlorate,Flurazepam Monohydrochloride,Staurodorm,Apo Flurazepam,Dihydrochloride, Flurazepam,Flurazepam Mono Perchlorate,Hydrochloride, Flurazepam,Mono-Perchlorate, Flurazepam,Monohydrochloride, Flurazepam
D000200 Action Potentials Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli. Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001570 Benzodiazepinones

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