CINP 2000 - Collegium Internationale Neuro-Psychopharmacologicum 22nd Congress.
At this large and varied meeting on neuropharmacotherapy, progress was reported on the newer more selective antipsychotics. The selective D(2) dopamine receptor partial agonist, aripiprazole (Otsuka Pharmaceutical Co Ltd) was recently proved effective over the medium term. The atypical antipsychotics generally, such as clozapine, have a good side effect profile and better patient compliance, even in Parkinson's disease (PD). Reboxetine (Pharmacia & Upjohn AB), having a far greater selectivity for norepinephrine reuptake inhibition than for serotonin or dopamine reuptake, is of particular value in treating depression. Paroxetine (Novo Nordisk A/S), a selective serotonin reuptake inhibitor (SSRI), has just completed a multicenter clinical trial, being effective in about 50% of cases of post-traumatic stress disorder. A meta-analysis of trials of other uptake inhibitors showed that ability to block serotonin (rather than norepinephrine) uptake correlated well with efficacy. Bipolar and other disorders were hoped to benefit from more selective agents in the future, the potential for which has been revealed through basic neurobiology, with, for example, only non-alpha7 nicotinic receptor subunits being expressed by those interneurons mediating nicotinic responses. An open label, 30-day study of a pyrrolopyrimidine, the corticotrophin releasing factor (CRF) type 1 receptor inhibitor, NBI-30775 (Neurocrine Biosciences Inc/Janssen Pharmaceutica NV) produced good antidepressant effects, but has had to be abandoned as a product due to indications of potential liver damage. Similarly, although glial-derived neurotrophic factor (GDNF) had proved ineffective in a 1999 trial for PD, due to failure to access the striatum, there was however much evidence to suggest that small molecule agonists of the TRK-B receptor should be effective. Of these, quinones such as L-783281 (Merck Research Laboratories) appear to activate all TRK subtypes by a common intracellular, rather than receptormediated action, which may limit their usefulness. Although such agents would have many potential applications, it is likely that highly selective receptor activation will be needed.
Ray
D E
DE
Medical Research Council Toxicology Unit, Hodgkin Building, University of Leicester, PO Box 138, Lancaster Road, Leicester, LE1 9HN, UK. der2@le.ac.uk