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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.

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5-HT(2C) receptors are predominantly localised in the brain and their dysregulation may contribute to particular symptoms of anxiety and depression. The marked affinity of several clinically established psychotropic agents sites (e.g., tricyclic antidepressants, clozapine, fluoxetine) for 5-HT(2C) receptor has generated interest in the therapeutic potential of selective, high affinity 5-HT(2C) receptor ligands. Like the selective serotonin re-uptake inhibitor (SSRI) fluoxetine, high affinity selective agonists such as Ro 60-0175 and Ro 60-0332 have potent in vivo activity in animal models suggestive of therapeutic action against depression, obsessive-compulsive disorder (OCD) and panic disorders. In contrast, 5-HT(2C) receptor antagonists such as SB-200646A or SB-221284 show signs of anxiolytic-like activity in tests for conditioned and phobic-like anxiety in rodents whereas they are inactive in tests indicative of antidepressant, antiOCD and antipanic activity. These results are consistent with an important hypothesis proposing that 5-HT has a complex, dual action on the neural mechanism of anxiety by either facilitating or inhibiting different kinds of anxiety in different brain regions. They also suggest that 5-HT(2C) receptor subtypes play an important role in the therapeutic properties of SSRIs. Certain 5-HT(2C) receptor antagonists may possess negative efficacy at 5-HT(2C) receptors and, as inverse agonists, may control constitutive receptor activity possibly characterising some psychopathological states. Receptor variants exist in the human population and indicate possible associations between somatic mutations in the 5-HT(2C) receptor and psychopathology or response to drug treatment. Selective 5-HT(2C) receptor ligands may offer innovative and improved therapeutic opportunities for the biological treatment of specific aspects of psychiatric syndromes.

This chapter takes note of the longstanding orientation Systemic Functional Linguistics (SFL) to discourse studies before moving to a more detailed and selective presentation of current developments in SFL with respect to discourse models, developing research methodologies, and applications to different domains. The reinterpretation of cohesion as discourse semantics (identification, negotiation, conjunction, and ideation) is reviewed with respect to metafunctions (textual, interpersonal, and ideational). This work on texture is then related to social context through the register variables tenor, field and mode alongside genre. The chapter then reviews recent SFL-inspired research that applies these models to analysis of discourse across languages, modalities of communication, and domains. Work done on school and workplace discourse has raised new questions about appropriate units of discourse structure and their relationship to register analysis. It is predicted that some of these questions may be answered by the development of improved software for discourse analyses affording greater specificity in mapping the relationships among genres.

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