RIMA is a term for reversible inhibitors of monoamine oxidase (MAO) with preference for MAO-A; moclobemide is a prototype of this new class of antidepressants and is a highly selective inhibitor of MAO-A in vitro. This inhibition is reversible by dialysis in vitro, which accounts for the dose-dependent duration of in vivo enzyme inhibition of 12-24 h. Moclobemide increases the content of serotonin, noradrenaline and dopamine in the brain, and decreases that of their deaminated metabolites. Its biochemical, neurological and behavioural effects indicate that it increases the extracellular concentration of the classic monoamine neurotransmitters/neuromodulators - in particular 5-HT. Potentiation of the cardiovascular effects of tyramine is less pronounced after taking moclobemide than after irreversible MAO-A inhibitors. Understanding of the physiological role of MAO and of the events that link inhibition of the enzyme with modulation of neuronal activities in the CNS remains incomplete. A major physiological role of intraneuronal MAO is to keep cytosolic amine concentration very low, to enable the neuronal monoamine carriers to produce a net inward transport of monoamines, and thereby to act as the first step in the termination of action of extracellular monoamines. MAO is likely to have a similar function in non-monoaminergic cells with respect to the monoamine carriers they contain. In addition to the classic monoamines, "trace" amines may become functionally active after MAO inhibition. An alternative role for MAO is that of a scavenger, preventing natural substrates from accumulating in monoaminergic neurons and interacting with storage, release, uptake and receptor function of monoamines.

This is an electrophysiological study in cats and rats of the imidazobenzodiazepinone derivative, Ro 15-1788, the first representative of specific benzodiazepine antagonists. (1) In unanaesthetized spinal cats, 1-10 mg kg-1 Ro 15-1788 i.v. did not affect segmental dorsal root potentials (DRPs), polysynaptic ventral root reflexes (VRRs), Renshaw cell responses to antidromic ventral root volleys and spontaneous gamma-motoneurone activity. However, at 1 mg kg-1 i.v., it antagonized the enhancement of DRPs as well as the depression of polysynaptic VRRs, Renshaw cell discharges and gamma-motoneurone activity induced by meclonazepam (0.1 mg kg-1 i.v.), diazepam (0.3 mg kg-1 i.v.) or zopiclone (1 mg kg-1 i.v.). The same dose of Ro 15-1788 failed to reduce similar effects of phenobarbital (10 mg kg-1 i.v.) on spinal cord activities. (2)In unanaesthetized "encéphale isole" rats, 3 mg kg-1 Ro 15-1788 i.v. abolished the decrease induced by 5 mg kg-1 midazolam i.v. of spontaneous multiunit activity (MUA) in the substantia nigra pars compacta, nucleus raphé dorsalis, nucleus locus coeruleus and the CAl area of the hippocampus dorsalis, but not the decrease produced by 10mg kg-1 pentobarbital i.v. Ro 15-1788 (12mg kg-1 i.v.) by itself did not affect MUA in the substantia nigra, but slightly depressed MUA in the other 3 areas. (3) In intact immobilized rats, the increase of power induced by 1 mg kg-1 flunitrazepam i.v. in the 0.5-48 Hz range of the electrocorticogram as well as in the 0.5-8 Hz, 8-32 Hz and 32-48 Hz frequency bands was transiently abolished by 5 mg kg-1 Ro 15-1788 i.v. (4) In unrestrained cats, 5 mg kg-1 Ro 15-1788 i.p. had no effect on the electrical threshold for eliciting a rage reaction evoked by electric hypothalamic stimulation, but abolished the threshold increase caused by 1 mg kg-1 diazepam i.p. These results are in line with biochemical and behavioural findings and support the selective antagonism by Ro 15-1788 of central effects of benzodiazepines through an interaction at benzodiazepine receptors.

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