Opiate modeling

Dobrenis K, Makman MH, Stefano GB (1995) Occurrence of the opiate alkaloid-selective p. receptor in mammahan microglia, astrocytes and Kupffer cells. Brain Res 686 239-248 Donahoe RM (2004) Multiple ways that drug abuse might influence AIDS progression clues from a monkey model. J Neuroimmunol 147 28-32... 

Donahoe RM, Byrd LD, McClure HM, Fultz P, Brantley M, MarsteUer F, Ansari AA, Wenzel D, Aceto M (1993) Consequences of opiate-dependency in a monkey model of AIDS. Adv Exp Med Biol 335(21-8) 21-28... 

The noradrenergic neurons of the locus ceruleus have provided a useful model system for the study of opiate addiction (see Ch. 56). Acutely, opiates inhibit these neurons, in part by inhibiting the cAMP pathway via inhibition of adenylyl cyclase. Chronically, these neurons become tolerant to opiates that is, their firing rates recover toward normal levels with continued exposure to the... 

Barr, M. et al., Escalating morphine exposures followed by withdrawal in feline immunodeficiency virus-infected cats A model for HIV infection in chronic opiate abusers, Drug Alcohol Depend.., 72, 141, 2005. 

Several opiate receptors have been identified on cells of the nervous systems of animals and humans, with mu (p), kappa (k), and gamma (y) subtypes being predominant. These classical opiate receptors are G- protein coupled 7-transmembrane molecules.27 Opiates predominantly affect immune responses directly by ligation of p, k, and y opiate receptors, as well as non-classical opiate-like receptors, on immune cells and indirectly by binding to receptors on CNS cells. Studies conducted in vitro with opiate-treated immune cells demonstrated receptor-mediated reduced phagocytosis, chemotaxis and cytokine and chemokine production. These effects are linked to modulation of host resistance to bacterial, protozoan, viral and fungal infections using animal models, cell lines and primary cells. 

Brandt, W., Barth, A., Holtje, H.D. A new consistent model explaining structure (conformation)-activity relationships of opiates with mu-selectivity, Drug Des. Discov. 1993, 10, 257-283. 

Figure 3. Proposed model for the action of opiates and opioid peptides on glyco-syltransferase activity. It is postulated that receptors for both opiates and neurotransmitters are linked to adenylate cyclase by a guanylnucleotide regulatory protein (GNRP). The presence of opiates or opioid peptides inactivates the cyclase, which normally activates a protein kinase-glycosyltransferase system, thereby initiating...

The opium alkaloids codeine and morphine served as models for the synthesis of naloxone, an important analog used to treat and diagnose opiate addicts, and also led to the discovery of endogenous opioids (enkephalins and endorphins) (see Chapter 47). Similarly, A9-tetrahydro-cannabinol (THC), the component of Cannabis sativa responsible for the central nervous system (CNS) effect, has also been found to reduce nausea associated with cancer chemotherapy (see Chapter 18). 

---