Brain tissue binding

Liu X, Smith BJ, Chen C, et al. Use of a physiologically based pharmacokinetic model to study the time to reach brain equilibrium an experimental analysis of the role of blood-brain barrier permeability, plasma protein binding, and brain tissue binding. J Pharmacol Exp Ther 2005 313(3) 1254—1262. 

Microtubule-associated proteins bind to microtubules in vivo and subserve a number of functions including the promotion of microtubule assembly and bundling, chemomechanical force generation, and the attachment of microtubules to transport vesicles and organelles (Olmsted, 1986). Tubulin purified from brain tissue by repeated polymerization-depolymerization contains up to 20% MAPs. The latter can be dissociated from tubulin by ion-exchange chromatography. The MAPs from brain can be resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). 

Monoamine concentrations or receptor binding in brain tissue post-mortem. 

A fourth important pharmacophoric element was established for the non-classical cannabinoid series in the form of a southern aliphatic hydroxyl group. Addition of this group to (192) resulted in the high-affinity CBi and CB2 receptor full agonist CP 55,940 (193) [129, 133], the tritiated form of which was used to first demonstrate specific cannabinoid binding sites in brain tissue [134]. Its enantiomer, CP 56,667 (194) has lower affinity for the CBi receptor (Table 6.17). 

Effects of Metabolism on Toxicity. Whether the toxic effects seen after exposure to diisopropyl methylphosphonate are caused by the parent compound or its metabolites is unknown. Studies of IMP A show that acute-duration exposure to IMPA results in reduced motor activity, prostration, and ataxia—effects also seen after exposure to diisopropyl methylphosphonate (EPA 1992). Other studies (Little et al. 1986, 1988) show that IMPA, the major metabolite of diisopropyl methylphosphonate, has an affinity for both lung and brain tissues and will bind to proteins in these tissues—effects that were not seen after exposure to diisopropyl methylphosphonate (EPA 1992 Little et al. 1988). These data and other data on the toxicity of IMPA neither support nor contradict the data found in the diisopropyl methylphosphonate studies, so it is not possible to attribute the effects after exposure to diisopropyl methylphosphonate to IMPA. Metabolites of IMPA other than MPA have not been identified. 

Lebel, L. A. Koe, B. K. (1992). Binding studies with the 5-HTlb receptor agonist [3H]CP-96,501 in brain tissues. Drug Devel. Res. 27, 253-64. 

Estradiol. The first neuroactive steroid receptor type to be recognized was that for estradiol [3]. In vivo uptake of [3H] estradiol, and binding to cell nuclei isolated from hypothalamus, pituitary and other brain regions, revealed steroid specificity closely resembling that of the uterus, where steroid receptors were first discovered [3]. Cytosolic estrogen receptors isolated from pituitary and brain tissue closely resemble those found in uterus and mammary tissue. A hallmark of the estrogen receptor is its existence... 

After whole-body autoradiography to study the distribution of " C-labeled chloroform in mice, most of the radioactivity was found in fat immediately after exposure, while the concentration of radioactivity in the liver increased during the postanesthetic period, most likely due to covalent binding to lipid and protein in the liver (Cohen and Hood 1969). Partition coefilcients (tissue/air) for mice and rats were 21.3 and 20.8 for blood 19.1 and 21.1 for liver 11 and 11 for kidney and 242 and 203 for fat, respectively (Corley et al. 1990). Arterial levels of chloroform in mongrel dogs reached 0.35-0.40 mg/mL by the time animals were in deep anesthesia (Chenoweth et al. 1962). Chloroform concentrations in the inhaled stream were not measured, however. After 2.5 hours of deep anesthesia, there were 392 mg/kg chloroform in brain tissue, 1,305 mg/kg in adrenals, 2,820 mg/kg in omental fat, and 290 mg/kg in the liver. 

Wiley JL, LaVecchia KL, Martin BR, Damaj MI (2002) Nicotine-like discriminative stimulus effects of bupropion in rats. Exp Clin Psychopharmacol 10 129-135 Williams M, Robinson JL (1984) Binding of the nicotinic cholinergic antagonist, dihydro-beta-erythroidine, to rat brain tissue. J Neurosci 4 2906-2911 Witkin JM, Dykstra LA, Carter RB (1982) Acute tolerance to the discriminative stimulus properties of morphine. Pharmacol Biochem Behav 17 223-228 Wooters TE, Bardo MT (2007) The monoamine oxidase inhibitor phenelzine enhances the discriminative stimulus effect of nicotine in rats. Behav Pharmacol 18 601-608 Wright JM Jr, Vann RE, Gamage TE, Damaj MI, WUey JL (2006) Comparative effects of dextromethorphan and dextrorphan on nicotine discrimination in rats. Pharmacol Biochem Behav 85 507-513... 

In vitro studies on binding of radiolabeled nicotine to pharmacological receptors in brain tissue... 

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