Handbook of experimental pharmacology
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Simple, rapid and inexpensive rodent models of nicotine physical dependence and withdrawal syndrome have proved useful for preliminary screening of smoking cessation treatments. They have led to an exponential increase of knowledge regarding the underlying neurobiological mechanisms of dependence and withdrawal syndrome. The human nicotine withdrawal syndrome in smoking cessation is variable and multidimensional, involving irritability, anxiety, depression, cognitive and attentional impairments, weight gain, sleep disturbances, and craving for nicotine. ⋯ For example, depression-like phenomena may involve alterations in mechanisms such as the mesolimbic dopamine pathway from the ventral tegmental area to the nucleus accumbens. Irritability and anxiety may involve alterations in endogenous opioid systems and other regions, such as the amygdala. This chapter reviews many additional anatomical, neurochemical, and developmental elements that impact nicotine physical dependence.
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Asthma is a heterogeneous disorder of unknown etiology that manifests as recurrent episodes of coughing, wheezing, and breathlessness. These symptoms are often debilitating and exacerbations usually are unexpected, resulting in work or school absences, limitations in activity, reduced quality of life, and personal and economic hardships. ⋯ However, asthma remains a global public health problem, and the hope is that newer therapies targeting specific biological mediators of asthma, particularly antibody-mediated therapies, offer exciting new modes to the control of this disease. We will review some of these therapies, with the majority of attention devoted to anti-IgE therapy which has been approved for treatment of adult and childhood asthma by the US Food and Drug Administration (FDA) since 2003.
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It is today generally accepted that anesthetics act by binding directly to sensitive target proteins. For certain intravenous anesthetics, such as propofol, barbiturates, and etomidate, the major target for anesthetic effect has been identified as the gamma-aminobutyric acid type A (GABA(A)) receptor, with particular subunits playing a crucial role. ⋯ For the less potent steroid anesthetic agents the picture is less clear, although a relatively small number of targets have been identified as being the most likely candidates. In this review, we summarize the most relevant clinical and experimental pharmacological properties of these intravenous anesthetics, the molecular targets mediating other endpoints of the anesthetic state in vivo, and the work that led to the identification of the GABA(A) receptor as the key target for etomidate and aminosteroids.
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Handb Exp Pharmacol · Jan 2008
ReviewPharmacokinetics and pharmacodynamics of GPI 15715 or fospropofol (Aquavan injection) - a water-soluble propofol prodrug.
Propofol (2,6-diisopropylphenol) is inadequably soluble in water and is therefore formulated as a lipid emulsion. This may have disadvantages when propofol is used to provide total intravenous anaesthesia or especially during long-term sedation. There has been considerable interest in the development of new propofol formulations or propofol prodrugs. ⋯ We found a significantly greater V(c), V(dss), significantly shorter alpha- and beta-half-life and a longer MRT (mean residence time) for propofol(G). The pharmacodynamic potency of propofol(G) appears to be higher than propofol when measured by EEG and clinical signs of hypnosis. In summary, GPI 15715 or fospropofol was well suited to provide anaesthesia or conscious sedation.