Toward a simulation approach for alkene ring-closing metathesis : scope and limitations of a model for RCM

A published model for revealing solvent effects on the ring-closing metathesis (RCM) reaction of di-Et diallylmalonate 7 has been evaluated over a wider range of conditions, to assess its suitability for new applications. Unfortunately, the model is too flexible and the published rate consts. do not agree with exptl. studies in the literature. However, by fixing the values of important rate consts. and restricting the concn. ranges studied, useful conclusions can be drawn about the relative rates of RCM of different substrates, precatalyst concn. can be simulated accurately and the effect of precatalyst loading can be anticipated. Progress has also been made toward applying the model to precatalyst evaluation, but further modifications to the model are necessary to achieve much broader aims

Serotonergic Agents and Alcoholism Treatment: A Simulation

Those with early-onset alcoholism may better respond to ondansetron (a 5-HT 3 receptor antagonist) than to selective serotonin reuptake inhibitor (SSRI) treatment, whereas those with late-onset alcoholism may present the reverse response pattern. Johnson and colleagues proposed a model that attempts to explain the observed treatment response patterns of those with early and late alcoholism onset by focusing on the influence of a common genetic variant in the serotonin transporter regulatory region (5-HTTLPR) on serotonin (5-HT) and dopamine (DA) system function. Methods : The present study formalizes and extends Johnson's descriptive model into a computer simulation consisting of differential equations. For each of 16 conditions defined by genotype, drinking status, diagnostic status, and drug treatment, data were generated by 100 simulation runs. Results : In every condition, the S/_ genotype (S/S and S/L) had higher extracellular 5-HT levels than did the L/L genotype. The S/_ genotype also had higher rates of postsynaptic DA firing than did the L/L genotype with the exception of the SSRI treatment condition, where the firing rates were similar. Drinking generally increased levels of extracellular 5-HT, reduced rates of presynaptic 5-HT firing, and increased rates of postsynaptic DA firing. Drinking produced increases in DA activation that were greater for the L/L genotype in the SSRI treatment condition and for the S/_ genotype in the ondansetron treatment condition. Conclusions : Genotype at 5-HTTLPR may influence relative reward of drinking alcohol while a person is under pharmacological treatment for alcoholism. Alternatively, 5-HTTLPR genotype may influence pathways of alcohol craving. Clinical studies should examine these hypotheses.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65336/1/01.ALC.0000098876.94384.0A.pd