Psychopharmacology
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Despite animal evidence that methylenedioxymethamphetamine (ecstasy) causes lasting damage in brain regions related to long-term memory, results regarding human memory performance have been variable. This variability may reflect the cognitive complexity of the memory tasks. However, previous studies have tested only a limited range of cognitive complexity. Furthermore, comparisons across different studies are made difficult by regional variations in ecstasy composition and patterns of use. ⋯ Results were consistent with the proposal that ecstasy-related memory deficits are more reliable on tasks with greater cognitive complexity. This could arise either because such tasks require a greater contribution from the frontal lobe or because they require greater interaction between multiple brain regions.
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The lack of potent, selective, brain penetrant Y(2) receptor antagonists has hampered in vivo functional studies of this receptor. ⋯ These results suggest that Y(2) receptors may not be critical for acute behaviors in rodents but may serve modulatory roles that can only be elucidated under specific situational conditions.
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Analgesic efficacy of opioids and dosing protocol have been shown to influence analgesic tolerance. ⋯ Taken together, intermittent and acute opioid agonist administration produces minimal tolerance compared to continuous infusion. Furthermore, there is an inverse relationship between analgesic efficacy and tolerance following continuous infusion. These results suggest that opioid analgesic tolerance may be increased when sustained release dosing formulations or continuous infusions are employed clinically.
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It was recently reported that administration of the metabotropic glutamate 2 and 3 (mGlu2/3) receptor agonist prodrug LY2140023 to schizophrenic patients decreased positive symptoms. However, at the single, potentially suboptimal, dose that was tested, LY2140023 trended towards being inferior to olanzapine on several indices of efficacy within the Positive and Negative Syndrome Scale. ⋯ Our results suggest that a single compound having both mGlu2/3 receptor agonist and 5-HT(2A) receptor antagonist activity, or coadministration of two compounds selective for these receptors, could be superior in terms of efficacy and/or reduced side-effect liability relative to an mGlu2/3 receptor agonist alone.
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The novel antidepressant, agomelatine, behaves as an agonist at melatonin MT(1) and MT(2) receptors and as an antagonist at serotonin (5-HT)(2C) receptors. In animal models and clinical trials, agomelatine displays antidepressant properties and re-synchronizes disrupted circadian rhythms. ⋯ Agomelatine possesses a distinctive EEG profile compared with melatonin, ramelteon, and S32006, possibly reflecting co-joint agonist and antagonist properties at MT(1)/MT(2) and 5-HT(2C) receptors, respectively.