SYMPOSIA
SYMPOSIA
SYMPOSIA
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Abstracts of the Invited Speakers<br />
[JS-07]<br />
Canadian College of Neuropsychopharmacology<br />
Symposium title: Advances in psychotropic drug development: Promising novel targets and agents for psychiatric disorders<br />
Recent advances in the neurochemistry of schizophrenia and potential targets for<br />
antipsychotic drug development<br />
Serdar Dursun, Glen Baker, Marnie Mackay<br />
Neurochemical Research Unit, University of Alberta, Edmonton, Canada<br />
E-mail: Dursun@ualberta.ca<br />
The dopamine hypothesis of schizophrenia has been a major influence for many years in stimulating research in schizophrenia<br />
and in assisting in the development of antipsychotic drugs. However, it has become obvious that other neurotransmitters and/or<br />
neuromodulators must also be involved. The antipsychotic drugs currently available are far from ideal and there is an urgent need to<br />
continue to search for new targets for potential antipsychotics.<br />
Much of the recent research on non-dopaminergic systems has focused on the amino acids glutamate and GABA, with the bulk of<br />
the results suggesting hypofunction of both in schizophrenia. Glutamate does not pass the blood-brain barrier readily and studies<br />
conducted to develop drugs that act at one or more of its multiple receptors have not, to our knowledge, yet produced potential new<br />
effective antipsychotics. Two other amino acids, glycine and D-serine, co-agonists at the NMDA glutamate receptor, have received<br />
considerable attention, and administration of these amino acids, usually in conjunction with currently available antipsychotics, have<br />
been reported in some studies to result in improvement of some symptoms of schizophrenia. However, these amino acids have to<br />
be administered in relatively high doses which may result in side effects such as peripheral neuropathies. There is now a great deal of<br />
interest in testing drugs that inhibit their uptake by neurons and/or glial cells (astrocytes and activated microglia), thus making increased<br />
levels of these amino acids available to interact with the NMDA receptor or, particularly in the case of D-serine, altering metabolism<br />
of the amino acid. This research also emphasizes the importance of glial cells. Microglia are also involved in immune responses and<br />
when activated release a number of proinflammatory cytokines that can result in some behavioural, cognitive, and neuroendocrine<br />
changes characteristic of schizophrenia. It is also of interest that there is now research indicating that there may be a dysfunction of<br />
oligodendrocytes and myelination problems in schizophrenia. Another exciting area of research with regard to schizophrenia is in<br />
the study of neuroactive steroids, rapid acting steroids which can act as positive or negative allosteric modulators at several types of<br />
neurotransmitter receptors, most notably GABA-A receptors and NMDA receptors. Plasma levels of several of these steroids are altered<br />
in a number of psychiatric disorders, including schizophrenia and some clinical studies suggest that pregnenolone may be a useful<br />
adjunctive agent in schizophrenia. Brain levels of some of these steroids have also been reported to be altered in laboratory animals<br />
following administration of currently available antipsychotics.<br />
In addition to the compounds mentioned above, potential interventions which may be added to the usual antipsychotic treatments<br />
include lamotrigine and minocycline. Furthermore, modulation of the nitric oxide pathway continues to gain considerable interest as a<br />
possible therapeutic target in the treatment of schizophrenia. We will report the results of an RCT double-blind crossover study on the<br />
addition of L-arginine, the precursor amino acid for nitric oxide, to usual treatment with antipsychotics in schizophrenic patients.<br />
Key words: Schizophrenia, antipsychotic development, glutamate, nitric oxide, D-serine, glycine, glia, neuroactive steroids<br />
Bulletin of Clinical Psychopharmacology 2011;21(Suppl. 2):S50<br />
Advances in antidepressant targets and drug development<br />
Glen B. Baker, Nicholas D. Mitchell, Jean Michel Le Melledo, Serdar Dursun<br />
Department of Psychiatry, University of Alberta, Edmonton, AB, Canada<br />
E-mail: glen.baker@ualberta.ca<br />
The biogenic amine hypothesis of depression, which suggests that depression is the result of a functional deficiency of noradrenaline<br />
(NA) and/or serotonin (5-hydroxytryptamine, 5-HT) at certain synapses in the brain, has had a major influence on research into the<br />
neurochemistry of depression for over fifty years, and most of the antidepressants currently available have an effect on one or both of<br />
these biogenic amines. However, it was obvious early on that other neurotransmitters or neuromodulators must also be involved, and the<br />
S50 Bulletin of Clinical Psychopharmacology, Vol: 21, Supplement: 2, 2011 - www.psikofarmakoloji.org