Trends in pharmacological sciences
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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.
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Trends Pharmacol. Sci. · Nov 2007
ReviewCGRP antagonists: unravelling the role of CGRP in migraine.
Migraine is a complex, debilitating neurovascular disorder. Although knowledge on the main molecular players is still incomplete, recent preclinical and clinical findings indicate that there is a clear correlation between migraine-associated headache and the release of the neuropeptide calcitonin gene-related peptide (CGRP). ⋯ The proven efficacy of this agent, and also the CGRP antagonist MK-0974, to alleviate acute migraine headache provided significant support for the hypothesis that CGRP has an important role in migraine pathophysiology. Moreover, the recently published results from Phase II trials are encouraging and suggest that this new type of drug might offer advantages over existing therapies for patients suffering from migraine and related headaches.
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Trends Pharmacol. Sci. · Oct 2006
ReviewChemokine receptors as therapeutic targets in chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is an increasing global health problem for which there are no effective disease-modifying therapies. COPD involves chronic inflammation of small airways and lung parenchyma, with the recruitment of inflammatory cells. ⋯ Several studies support the implication of several chemokines and their receptors in COPD, including chemokine receptors CXCR2 and CXCR3, with small-molecule receptor antagonists that are in development being potential anti-inflammatory therapies. Such a pharmacological strategy would provide a mechanism with which to inhibit leukocyte recruitment and, hence, reduce the inflammatory profile in COPD, which is currently unaffected by pharmacotherapy.
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Trends Pharmacol. Sci. · Jun 2006
ReviewRole of delivery and trafficking of delta-opioid peptide receptors in opioid analgesia and tolerance.
Changes in the number of receptors on the cell surface lead to modulations of physiological functions and pharmacological responses of neurons. Recent studies show that delta-opioid peptide (DOP) and mu-opioid peptide (MOP) receptors have distinct subcellular localizations in neurons. In nociceptive small neurons in the dorsal root ganglia, DOP receptors are sorted into neuropeptide-containing secretory vesicles, enabling the stimulus-induced cell surface expression of these receptors. ⋯ The physical interaction between DOP receptors and MOP receptors seems to be an important mechanism for the modulation of receptor functions. Experiments in animals show that MOP-receptor-mediated spinal analgesia is enhanced and morphine tolerance does not develop when DOP receptor functions are pharmacologically or genetically attenuated. Thus, the delivery and trafficking of DOP receptors are crucial processes that modulate opioid analgesia and tolerance.
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Multiple arousal systems maintain waking through the actions of chemical neurotransmitters that are released from broadly distributed nerve terminals when the neurons fire. Among these, noradrenaline-, histamine- and orexin-containing neurons fire during waking with behavioral arousal, decrease firing during slow-wave sleep (SWS) and cease firing during paradoxical sleep (PS), which is also known as rapid-eye-movement sleep. ⋯ The reciprocal activities and interactions of these wake-active and sleep-active cell groups determine the alternation between waking and sleeping. Selective enhancement and attenuation of their discharge, transmitter release and postsynaptic actions comprise the substrates for the major stimulant and hypnotic drugs.