Alkaloids, opioid

As structure and function are intimely related. X-ray crystallography is the most comprehensive technique, which elucides the three-dimensional structure of the molecule. X-ray crystallographic study provides an accurate and complete chemical characterization of the compound. This method has successfully been used for the analysis of such opioid alkaloids as morphine and has evaluated as very precise and even suitable for the research of novelizations of compounds. The use of this method can also help the estimation of the receptor, because compound structure is important in binding to the receptor. 

Opioid alkaloids (eg, morphine) produce analgesia through actions at receptors in the central nervous system (CNS) that contain peptides with opioid-like pharmacologic properties. The general term currently used for these endogenous substances is endogenous opioid peptides. 

The opioid alkaloids are classic examples of non-peptide ligands that have later been discovered to be mimetics of endogenous peptides. For example, morphine 5 (Figure 1.4.3) imitates the effect of flexible peptides, for example Met-enkephalin 4, at the common recognition site of the receptor for both compounds... 

Shen and Crain [13] tested the effects of biphalin on naive and chronic morphine-treated dorsal root ganglion (DRG) neurons in cell culture. At low (pM-nM) concentrations, most mu, delta, or kappa opioid peptides as well as morphine and other opioid alkaloids elicit dose-dependent excitatory prolongation of the calcium-dependent component of the action potential duration (APD) of many mouse sensory DRG neurons. In contrast, application of the same opioids at higher (pM) concentrations results in inhibitory shortening of the APD [14]. Biphalin at a low concentration elicits only dose-... 

Kampa, M., Bakogeorgou, E., Hatzoglou, A., Damianaki, A., Martin, P.-M., and Castanas, E. 1997. Opioid alkaloids and casomorphin peptides decrease the proliferation of prostatic cancer cell lines (LNCaP, PC3 and DU145) through a partial interaction with opioid receptors. Fur. J. Pharmacol 335, 255-265. 

Schwyzer R. Estimated membrane structure and receptor subtype selection of an opioid alkaloid-peptide hybrid. Inti J Peptides Protein Res 1988 32,476-483. 

The roles of calcium and calcium antagonists in the central nervous system are dealt with in the next two chapters. From Dr. Leong Way s laboratory comes an overview of the mechanism of interaction between calcium and opioid alkaloids and peptides, while Dr. Ferrendelli reviews... 

Pharmacologic Consequences of Calcium Interactions with Opioid Alkaloids and Peptides... 

Practically all the opioid alkaloids and most of their synthetie structural analogues are precisely the mu selective agonists. 

The opioid peptides isolated from mammalian tissue are known collectively as endorphins, a word that is derived from a combination of endogenous and morphine. The opioid alkaloids and all of the synthetic opioid derivatives are exogenous opioids. Interestingly, the isolation of morphine and codeine in small amounts has been reported from mammalian brain (9). The functional significance of endogenous morphine remains unknown. 

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