Anxiolytics endogenous

Dmg receptors represent another type of receptor family. The central nervous system (CNS) effects of the anxiolytic, diazepam, and the psychotropic actions of the caimabiaoids and phencycUdine have resulted ia the identification of specific receptors for these molecules. This has resulted ia the search for an endogenous ligand for these receptors. Thus, ia these situations, the pharmacological action has preceded the discovery of the receptor which, ia turn, has provided clues ia several iastances to the endogenous ligand. 

Marsicano G, Wotjak CT, Azad SC, Bisogno T, Rammes G, Cascio MG, Hermann H, Tang J, Hofmann C, Zieglgansberger W, Di Marzo V, Lutz B (2002) The endogenous cannabinoid system controls extinction of aversive memories. Natme 418 530-534 McKeman R, Rosdahl T, Reynolds D, Sur C, Wafford K, Atack J (2000) Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABA-A receptor alpha-1 subtype receptors. Nat Neurosci 3 587-592... 

Evidence that NPY mediates anxiety is accumulating (Wahlestedt and Reis 1993]. The behavioral profile of centrally administered NPY includes stimulation of appetite and anticonflict prominence (B. G. Stanley and Leibowitz 1985]. Gehlert [1994] suggested that NPY functioning as a putative endogenous anxiolytic is mediated at the Y1 receptor subtype. 

The use of benzodiazepines in anxiety disorders represents a difficult issue because of the well-known addictive properties of this substance class furthermore, the depressogenic lability of benzodiazepines represents a major problem in the treatment of generalized anxiety disorders, in which concomitant depressive symptoms occur in up to 50% of patients [Gulley and Nemeroff 1993 Rickels and Schweizer 1993]. Therefore, a compound mimicking endogenous anxiolytic effects, and that might further possess potential antidepressive properties, is warranted. Neuroactive steroids could represent such a substance class. However, the following issues need to be addressed in this respect ... 

Bitran D, Hilvers RJ, Kellogg CK Anxiolytic effects of 3a-hydroxy-5a-pregnan-20-one, endogenous metabolite of progesterone that are active at the GABA receptor. Brain Res 561 157-161, 1991... 

Crawley JN, Glowa JR, Majewska MD, et al Anxiolytic activity of an endogenous adrenal steroid. Brain Res 398 382-385, 1986... 

There is some evidence to suggest that the benzodiazepines exist not only in plants such as the potato but also in the mammalian brain, including the brains of individuals who have never taken benzodiazepine anxiolytics or hypnotics. While such findings are still controversial, they do point to the possibility that the benzodiazepines are endogenous modulators of the GABA receptor and that a defect in their synthesis may have a role to play in the aetiology of anxiety disorders. 

There is inadequate activity of an endogenous anxiolytic ligand. 

Patel, S., and Hillard, C.J. (2006). Pharmacological evaluation of cannabinoid receptor ligands in a mouse model of anxiety Further evidence for an anxiolytic role for endogenous cannabinoid signaling.. Pharmacol. Exp. Ther. 318, 304-311. 

Sigma receptor ligands bind to metabotropic GPCRs as well as ionotropic cr-Rs (Chapter 3). Endogenous ligands for cr-Rs include some opiates. Sigma-R activation can have antitussive, anxiolytic and ulceroprotective effects. Hypericin from Hypericum perforatum (St John s wort) is... 

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