Trends in pharmacological sciences
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Trends Pharmacol. Sci. · Apr 2008
ReviewMechanism-based pharmacokinetic-pharmacodynamic (PK-PD) modeling in translational drug research.
The use of pharmacokinetic-pharmacodynamic (PK-PD) modeling in translational drug research is a promising approach that provides better understanding of drug efficacy and safety. It is applied to predict efficacy and safety in humans using in vitro bioassay and/or in vivo animal data. Current research in PK-PD modeling focuses on the development of mechanism-based models with improved extrapolation and prediction properties. ⋯ The different terms represent: target-site distribution, target binding and activation and transduction. Ultimately, mechanism-based PK-PD models will also characterize the interaction of the drug effect with disease processes and disease progression. In this review, the principles of mechanism-based PK-PD modeling are described and illustrated by recent applications.
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Impulsivity is a heterogenous phenomenon encompassing several behavioural phenomena that can be dissociated neuroanatomically as well as pharmacologically. Impulsivity is pathological in several psychiatric disorders including attention-deficit/hyperactivity disorder (ADHD), drug addiction and personality disorders. Pharmacological agents alleviating impulsivity therefore might substantially aid the treatment of these disorders. ⋯ Accumulating evidence also points towards an important role of brain dopamine and noradrenaline systems in impulsive behaviour, consistent with the therapeutic efficacy of amphetamine, methylphenidate and atomoxetine in ADHD. However, recent findings also implicate glutamate and cannabinoid neurotransmission in impulsivity. In this review, we will discuss some of the recent developments in the neuropharmacological manipulation of impulsive behaviour.