Handbook of experimental pharmacology
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Nonimmobilizing, inhalational anesthetic-like compounds are experimental agents developed as a tool to investigate the mechanism of action of general anesthetics. Clinically used for more than 150 years, general anesthesia has until now defied all attempts to formulate a theory of its mechanisms that would link, in an uninterrupted logical chain, observations on the molecular level-via effects on the cellular and network levels-to the in vivo phenomenon. Nonimmobilizers, initially termed nonanesthetics, are substances that disobey the Meyer-Overton rule. ⋯ This discovery required not only the introduction of the more precise term "nonimmobilizers," but also excluded one important component of anesthesia, i.e., amnesia, from application of the algorithm. On the other hand, compared to inhalational anesthetics, nonimmobilizers interact with relatively few molecular targets, also limiting the usefulness of the nonimmobilizer algorithm. Nevertheless, nonimmobilizers have not only yielded useful results but can, by virtue of those very properties that make them less than ideal for anesthesia research, be used as experimental tools in the neurosciences far beyond anesthetic mechanisms.
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Handb Exp Pharmacol · Jan 2007
ReviewPhospholipase C-coupled receptors and activation of TRPC channels.
The canonical transient receptor potential (TRPC) cation channels are mammalian homologs of the photoreceptor channel TRP in Drosophila melanogaster. All seven TRPCs (TRPC1 through TRPC7) can be activated through Gq/11 receptors or receptor tyrosine kinase (RTK) by mechanisms downstream of phospholipase C. ⋯ TRPC channels have been proposed to be activated by a variety of signals including store depletion, membrane lipids, and vesicular insertion into the plasma membrane. Here we discuss recent developments in the mode of activation as well as the pharmacological and electrophysiological properties of this important and ubiquitous family of cation channels.
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The discovery of the endogenous systems of analgesia has produced a large amount of research aimed at investigating their biochemical and neurophysiological mechanisms and their neuroanatomical localization. Nevertheless, the neurobiological acquisitions on these mechanisms have not been paralleled by behavioural correlates in humans--in other words, by the understanding of when and how these endogenous mechanisms of analgesia are activated. ⋯ By contrast, today the placebo analgesic effect represents one of the best-described situations in which this endogenous opioid network is naturally activated in humans. Therefore, not only is placebo research helpful towards improving clinical trial design and medical practice, but it also provides us with a better understanding of the endogenous mechanisms of analgesia.
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Handb Exp Pharmacol · Jan 2007
ReviewLimitations of pharmacotherapy: behavioral approaches to chronic pain.
Pharmacotherapy is most appropriate in acute pain, whereas in chronic pain states behavioral approaches or a combination of behavioral treatment and pharmacotherapy is more appropriate. In this chapter we first describe the role of learning and memory as well as other psychological factors in the development of chronic pain and emphasize that chronic pain must viewed as the result of a learning process with resulting central neuroplastic changes. We then describe operant behavioral and cognitive-behavioral treatments as well as biofeedback and relaxation techniques and present innovative treatment procedures aimed at altering central pain memories. We complete the section with a discussion of combined behavioral and pharmacological approaches and an interdisciplinary view.
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Handb Exp Pharmacol · Jan 2007
ReviewAntipyretic analgesics: nonsteroidal antiinflammatory drugs, selective COX-2 inhibitors, paracetamol and pyrazolinones.
Antipyretic analgesics are a group of heterogeneous substances including acidic (nonsteroidal antiinflammatory drugs, NSAIDs) and nonacidic (paracetamol, pyrazolinones) drugs. Moreover, various selective cyclooxygenase-2 (COX-2) inhibitors with improved gastrointestinal tolerability as compared with conventional NSAIDs have been established for symptomatic pain treatment in recent years. The present review summarizes the pharmacology of all of these drugs with particular emphasis on their rational use based on the diverse pharmacokinetic characteristics and adverse drug reaction profiles. Referring to the current debate, potential mechanisms underlying cardiovascular side effects associated with long-term use of COX inhibitors are discussed.