Receptors activated solely by synthetic

Scearce-Levie K, Coward P, Redfem CH, Conklin BR. Engineering receptors activated solely by synthetic ligands (RASSLs). Trends Pharmacol Sci 2001 22(8) 414-420. 

K. Scearce-Levie, P. Coward, C.H. Redfern, B.R. Conklin, Tools for dissecting signaling pathways in vivo receptors activated solely by synthetic ligands, Meth. Enzymol. 2002, 343, 232-248. 

It clearly appears that if the endocannabinoid system really plays a role in the physiopathology of schizophrenia, the activation of CBj receptors does not seem to be a crucial point. Interestingly, CBi is not the sole CB receptor subtype expressed in the brain. Some studies using CB, KO mice supported the existence of G-protein-coupled non-CBj and non-CBj cannabinoid receptors, sensitive to endocannabinoids, synthetic agonists, and rimonabant (Di Marzo et al., 2000 Breivogel et al., 2001 Pride et al., 2003). In addition, anandamide has been found to activate both CB, and vanilloid VR, receptors (for review see Di Marzo et al., 2002). However, the localizations and functions of such types of receptors are unclear, and their putative role in schizophrenia remains to be demonstrated. Although cannabis use appears to be neither a sufficient nor a necessary cause for psychosis, the current status of research on cannabis-associated psychosis (Leweke et al., 2004) is inconclusive, and further research is needed to understand the mechanisms by which cannabis is associated with psychosis. 

As already mentioned, in contrast to the cobaltocenium moiety, the ferrocene derivatives represent neutral redox-active receptors for anions. As we are losing coulombic interactions, the complexation is mediated solely via hydrogen bonding. Consequently, the corresponding association constants can be evaluated only in HB non-competitive solvents and they are usually much lower when compared with those of cobaltocenium derivatives. This apparent disadvantage is compensated by the much higher synthetic potential of ferrocene (commercial availability of many derivatives, much easier synthetic handling) and the excellent electrochemical properties of this compound. 

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