F C Colpaert

..The changes of mnesic state that are likely associated with excessively labile cholinergic neurotransmission may conceivably cause the complex disabilities of Alzheimer's disease...

..Paralleling patient-controlled analgesic drug intake, FSA offers a specific measure allowing the dynamic effects of neurobiological agents to be studied in this unique animal model of persistent nociceptive pain...

..It is suggested that depression may in part be acquired in the course of ontogeny and may be available for retrieval in the same but not in other states; various biological rhythms conceivably define such states...

..The transduction mechanism defines a continuously evolving process; the process's most peculiar feature is that it makes any input generate not one but two outcomes that are paradoxical, or opposite in sign...

..These concepts enabled the discovery of the antipsychotic risperidone, a unique full antagonist of the interoceptive effects of LSD...

..F 13640-induced analgesia persisted during this post-treatment period. The data offer initial evidence that high-efficacy 5-HT(1A) receptor activation produces an unprecedented curative-like action on pathological pain...

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..The data also indicate that F 13640 may be effective with opioid-resistant pain. It further is suggested that opioid addiction may represent self-therapy of opioid-induced pathological pain...

..Although awaiting proof-of-concept evidence in humans, high-efficacy 5-HT(1A) receptor activation may uniquely challenge the opioids for pain therapy...

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..The results document the utility of using [35S]GTP gamma S binding studies to assess agonist efficacy, and to characterize 5-HT1B/D receptor ligands as apparently neutral antagonists and inverse agonists at the G-protein level...

..In conclusion, the fusion protein approach opens perspectives to quantify intrinsic activities of ligands under controlled experimental conditions of a fixed receptor:G alpha15 protein ratio of 1...

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..The conditions identified here appear appropriate for future studies of these four compounds in rat models of chronic pain and neuropathic allodynia...

..e., forepaw treading) of the 5-HT syndrome which 8-OH-DPAT also induces...

..In conclusion, the amplitude of the Ca(2+) responses induced by partial, but not that to fuller 5-HT(1A) receptor agonists, is affected by the Thr(149)Ala mutation of the 5-HT(1A):G(alpha)(15) fusion protein...

..The observed spectrum of intrinsic activities for the various ligands suggests that pure, neutral antagonists are rather uncommon in this specified alpha(2A)-AR system...

..4. In conclusion, kinetic analyses of agonist : antagonist interactions at the alpha(2C) AR demonstrate a wide spectrum of partial to complete antagonism of the low-magnitude Ca(2+) response for structurally related alpha(2) AR ligands...

..Thus, the combination of the ACAT inhibitor F 12511 with atorvastatin can represent a better approach than either agent alone to regulate lipoprotein metabolism in certain pathophysiological situations...

..These Ca2+ data indicate that putative DA antagonists act differently, in particular, at the DA-bound D(2short) receptor...

..Most antagonists may actually possess partial agonist properties at the alpha2 AR subtypes, which are facilitated by the same mutation in the distal portion of their third intracellular loop...

..The observed attenuation of dopamine-mediated Ca(2+) signal generation with different decay-times may underlie distinct properties of the dopaminergic ligands...

..In conclusion, these Ca(2+) data suggest that multiple activation binding sites exist for these ligands at the alpha(2A) AR, and that their activation may be affected in different ways by the mutations being investigated...

..0. These data indicate that a single ligand may display different magnitudes of activation at the alpha(2A) AR subtype coupled to chimeric G(alphao) proteins under controlled conditions of alpha(2A) AR: G(alphao)-protein expression...

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..In conclusion, human 5-HT1D receptors are involved in the growth of C6-glial/5-HT1D cells. This cellular response is highly sensitive to the intrinsic activity of compounds at 5-HT1D receptors...

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..The findings indicate that with opioid signaling systems, transduction mechanisms operate that may cause the sign of the effect to reverse not only when activation is discontinued but also whilst it is maintained at a constant magnitude...

..Activation of post-synaptic 5-HT(1A) receptors may provide enhanced therapy against depression. We describe the signal transduction profile of F15599, a novel 5-HT(1A) receptor agonist...

..The observed heterogeneity of Ca(++) responses produced by different ligands at wt and mutant alpha(2A) AR may be explained by assuming the existence of multiple ligand activation binding sites at the alpha(2A) AR...

..A 28-day subcutaneous infusion with dexefaroxan (0.63, 2.5, and 10 mg rat(-1) day(-1)), starting from the moment of the devascularization, protected against this spatial memory deficit...

..Thus, because tolerance did not develop to the morphine state, an increasingly large body of engrams became encoded in that state, rendering retrieval increasingly dependent...

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..These data indicate that the alpha(2) AR ligand RX 831003 behaves as a protean agonist at the alpha(2A) AR and that its activity is highly dependent on the co-expressed G(alpha) protein subunit...

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..Extensive parametric studies are needed to unravel the apparently subtle conditions that govern the occurrence and features of the state dependence produced by various CNS compounds...

..In conclusion, the pharmacology of the cloned 5-HT1D receptor subtype seems, unlike the 5-HT1B receptor subtype, conserved among various mammal species such as the human, guinea pig, and rat...

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..Unlike the opioid, remifentanil, F 13640 caused no hyperalgesia with ongoing postoperative pain, and should remain effective with protracted postoperative use...

..Together, these results suggest the existence of distinct and agonist-specific signalling states of this receptor...

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..The stable effects of F 13640 during the second week of treatment surpassed those of morphine and were not improved by the addition of morphine to F 13640...

..These results demonstrate that F 13640 induces hyperalgesia and/or analgesia with a time course that parallels the occupancy of 5-HT(1A) receptors and the presence of the compound in blood and brain...

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..These results show that THP-1 macrophages could be an useful cellular model to investigate effects of compounds on plaque vulnerability through MMP-9 activity...

..These findings demonstrate that 5-HT(1A) receptor agonists can act in the spinal cord to produce both hyper- and hypo-algesic effects and play a major role in the opioid analgesia and tolerance...

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..The present data extend recent evidence that high-efficacy 5-HT(1A) receptor activation constitutes a new mechanism of central analgesia the spectrum of which may also encompass trigeminal neuropathic pain...

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..Since donitriptan also increased pVCO(2), an effect upon cerebral oxygen consumption and metabolism is suggested in addition to cranial vasoconstriction, which may be relevant to its headache-relieving effects...

..These results show that EAhy926 endothelial cells are an adequate tool to substantiate and characterize inflammatory impacts of PPAR activators...

..Producing the mirror opposite of morphine's neuroadaptive actions, F 13640 causes an analgesia that becomes more powerful with chronic administration, and this at the expense of the initial hyperalgesia which it may also produce...

..The data presented here suggest that F 13640 may perhaps offer a lasting treatment of trigeminal neuralgia...

..e., F 13640) may in a selective way induce responses that may be not at all be achieved with other ligands (i.e., buspirone). In conclusion, the pharmacology of 5-HT1A receptor ligands seems to be codetermined by the effector pathway...

..Importantly, the preemptive effect of F 13640 persisted for 2 months after treatment was discontinued. The data warrant the study of the possible effects of the early administration of F 13640 in patients sustaining spinal cord injury...

..Cardiac VGSC blockers such as KC 12291, which block cardiac VGSCs in atypical fashion by effectively inhibiting the sustained component of Na+ current, represent, therefore, promising potential antiischemic and cardioprotective drugs...

..The data may elucidate tacrine's limited therapeutic efficacy insofar as scopolamine's mnesic actions both model human pathology and are due to scopolamine producing state-dependence...

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..We conclude that halothane at high concentrations (1.5-2%) seems to play a predominant inhibitory role via spinal multireceptors on ventral horn (VH) motor neurons, and less on DH sensory WDR neurons, of the spinal cord...