Jean Bidlack

..8-Carboxamidocyclazocine is a novel, long-acting benzomorphan, which possesses pharmacological properties that are distinct from the properties of cyclazocine...

..As suggested by animal studies, the PB withdrawal seizures and increase in aura frequency in this patient may be explained by changes in her levels of GABA(A) receptor subunits...

..In transfected systems, opioid receptors have been shown to dimerize with chemokine and cannabinoid receptors, resulting in crosstalk between different types of receptors...

..MCL-145 also acted as a mu antagonist, as measured by the inhibition of morphine-induced antinociception...

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..These data demonstrate an approach for modulation of G protein-coupled receptor signaling that may represent an important therapeutic strategy...

..3 nmol and 3.0 nmol, respectively)...

..These findings demonstrate the feasibility of using rAd5 vectors to express opioid receptors at high densities, which may facilitate opioid receptor studies...

..Understanding the mechanism behind the reduction of proinflammatory cytokine production by opioids may lead to the development of more effective therapeutics for inflammatory diseases...

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..The optimal 'degree of glycosylation' for the DAMGO peptide message appears to be between 1.25 and 1.75 g.u. (hydrodynamic g.u.), or 0.75 and 0.90 in terms of the surface-derived amphipathicity values...

..Functional activities of these compounds were measured in the [35S]GTPgammaS binding assay, illustrating that all of these ligands were kappa agonists. At the mu receptor, compounds 11 and 12 were mu agonist/antagonists...

..High binding affinity to all three opioid receptors were observed for the N-(2-naphthylethyl) analogue of 8-CAC...

..A preliminary SAR revealed that affinity is very sensitive to substitution on the formamide appendage...

..In addition to the results from this study strongly supporting this pharmacophore hypothesis, a number of novel compounds with high affinity to opioid receptors have been identified...

..Several derivatives were shown to have intrinsic opioid-receptor-mediated activity in [(35)S]GTPgammaS assays...

..At the mu receptor, compounds 1b, 1c, 2b, and 3b were agonists, while compounds 2c-e and 3c-e were mu agonists/antagonists...

..MCL 450 represents a useful starting point for the synthesis of other multiple opioid ligands endowed with analgesic properties with low tolerance and dependence...

..High binding affinity to mu, kappa, and delta opioid receptors was observed for the 8-[N-(4'-phenyl)-phenethyl)carboxamido] analogue...

..The opioid activities were relatively low, and the alpha3beta4 nicotinic acetylcholine receptor activities were found to correlate with in vivo antiaddictive activities...

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..High affinity for opioid receptors was observed for the 8-CSNH2 and 8-NHCHS analogues indicating that these groups are isosteric with not only the 8-OH but with the previously synthesized 8-CONH2 and 8-NHCHO cyclazocine derivatives...

..g., K(i)=0.052nM for mu) has been observed in the rationally designed naltrexone analogue 5. SAR and physical data supports the hypothesis that the 4-OH group of 5 stabilizes the 3-carboxamido group in the putative bioactive conformation...

..However, non-selective effects of 8-CAC on food-maintained responding and tolerance to 8-CAC effects on cocaine self-administration may limit its potential for the treatment of cocaine dependence...

..The mu, delta, and kappa receptor binding affinity of a series of N-substituted 3-deoxynormorphines 6 and 7 and N-substituted 3-deoxydihydronormorphines 8-11 was also determined...

..To design and synthesize new chiral 8-(substituted) amino-analogues of 3-[(tetrahydro-2-furanyl)methyl] benzomorphans, to expand knowledge of the structure-activity relationship (SAR) for 8-aminobenzomorphan...

..These studies will results in a better understanding of how opiates modulate immunocompetence and may help explain why heroin addicts are very susceptible to viral infection...

..The experiments described in this proposal will result in an understanding of the high affinity binding sites and second messenger systems by which kappa opioids can influence immunocompetence...

..The characterization of novel cyclazocine derivatives will identify potential medications for treating cocaine and heroin abuse and will suggest the basic mechanisms responsible for the drug's action. ..

..In addition, because HHV-6 and -7 infect both T lymphocytes and cells of the human central nervous system, this could result in the expression of a novel opioid receptor that is only present in the human neurons and T lymphocytes. ..

..These studies will lay the foundation for determining the cellular mechanisms by which opioids alter immune function and immunological responses to viral infection, including AIDS. ..

..We feel that participation by many pre- and postdoctoral trainees has resulted and is likely to continue to result in recruiting promising scientists to a career of drug abuse research. ..

..We feel that participation by many pre- and post-doctoral trainees has resulted and is likely to continue to result in recruiting promising scientists to a career of drug abuse research. ..

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..This Training Program has served and will continue to serve as the focus for the training and research activities in drug abuse within the University and surrounding community. ..

..This Training Program has served and will continue to serve as the focus for the training and research activities in drug abuse within the University and surrounding community. ..

..We feel that participation by many pre- and post- doctoral trainees is likely to continue to result in recruiting promising scientists to a career of drug abuse research. ..

..Based on the amino acid sequences, oligonucleotide probes will be synthesized, and used to screen cDNA libraries, in order to ultimately clone the mu opioid receptor...

..Second messenger effects such as adenylate cyclase and the Na+/H+ antiporter exchange will be studie to determine if PKC is exerting its effect through either of these second messenger systems...