Neuroprotective effects

CJ-Receptors are localized ia the brain stem and limbic stmcture, regions associated with endocrine function (76). In the periphery, CJ-receptors are found in the Hver, heart, ileum, vas deferens, and on lymphocytes and thymocytes. Although there is insufficient evidence to clearly define the functional role of CNS CJ-sites, based on the effects of PCP and the interaction of haloperidol with CJ-sites, CJ-receptor ligands may be antipsychotics or used for the treatment of substance abuse. Several CJ-receptor ligands have shown neuroprotective effects in vivo. Ifenprodil (315) and CNS 1102 (316) are being developed for treatment of stroke (Table 18). 

Koob GF, Mason BJ, De Witte P, et al Potential neuroprotective effects of acamprosate. Alcohol Clin Exp Res 26 386—592, 2002... 

Kamei K, Maeda N, Nomura K, Shibata M, Katsuragi-Ogino R, Koyama M, Nakajima M, Inoue T, Ohno T, Tatsuoka T. Synthesis, sar studies, and evaluation of 1,4-benzoxazepine derivatives as selective 5-htla receptor agonists with neuroprotective effect discovery of piclozotan. Bioorg Med Chem 2006 14 1978-1992. 

Marinov MB, Harbaugh KS, Hoopes PJ, Pikus HI, Harbaugh RE. Neuroprotective effects of preischemia intraarterial magnesium sulfate in reversible focal cerebral ischemia. J Neurosurg 1996 85 117-124. 

Du C, Hu R, Csemansky CA, Liu XZ, Hsu CY, Choi DW. Additive neuroprotective effects of dextrorphan and cycloheximide in rats subjected to transient focal cerebral ischemia. Brain Res 1996 718 233-236. 

Finally, the fact that anthocyanins can reach the brain represents a beginning of an explanation of the purported neuroprotection effects of anthocyanins. Anthocyanins may be eliminated via urinary and biliary excretion routes. " The extent of elimination of anthocyanins via urine is usually very low (< 0.2% intake) in rats and in humans, indicating either a more pronounced elimination via the bile route or extensive metabolism. As mentioned earlier, in the colon, non-absorbed or biliary excreted anthocyanins can be metabolized by the intestinal microflora into simpler break-down compounds such as phenolic acids that may be (re)absorbed and conjugated with glycine, glucuronic acid, or sulfate and also exhibit some biological... 

Yu, T.L., Gu, J.L., Lysko, P.G., Cheng, H.Y., Barone, F.C. and Feuerstein, G. (1992). Neuroprotective effects of phenyl-f-butyl-nitrone in gerbil global brain ischemia and in cultured rat cerebellar neurons. Brain Res. 574, 193-197. 

Cannabidiol has low affinity for CBi and CB2 receptors and is not psychoactive, but has nevertheless shown a number of pharmacological activities of its own including anti-inflammatory and neuroprotective effects. Some side chain-modified cannabidiol derivatives have also been evaluated for can-nabinoid receptor affinity and these are shown in Table 6.15. 

It has been revealed that cannabinoids exhibit neuroprotectant activities in both in vitro and in vivo models [249]. The neuroprotective effects are mainly based on regulation of transmitter release, modulation of calcium homeostasis, anti-oxidant properties and modulation of immune responses. A number of neurological disorders, including brain trauma, cerebral ischaemia, Parkinson s disease and Alzheimer s disease represent possible therapeutic areas for cannabinoids with neuroprotective properties. Cannabinoids are also suggested to have potential against glaucoma due to their neuroprotective nature and lowering of intraocular pressure [250]. 

Mechanism of Action The mechanism of action of divalproex is not well understood. It is known to affect ion transport and enhances the activity of y-aminobutyric acid. Like lithium, it also has possible neuroprotective effects through enhancement of brain-derived neurotrophic factor.31... 

Have the neuroprotective effects of this unique cation been overlooked Biol Psych 1999 46 929-940. 

Manji HK, Chen G. Lithium upregu-lates the cytoprotective protein bcl-2 in vitro and in the CNS in vivo, a role for neurotrophic and neuroprotective effects in manic-depressive illness. J Clin Psychiatry 2000 61 82-96. 

Pteridines have been prepared in good yields from 6-amino-5-nitrosouracils with Meldrum s acid in the presence of piperidine as catalyst under thermolytic conditions <06SC3085>. Novel 6-formylpterin derivatives have been synthesized and their neuroprotective effects studied <06OBC1811>. 

Inhibitors of MLK (MKKK) [27], MKK4, 7 and JNK [6,28,29] have been disclosed to date. CEP-1347, a semi-synthetic analog of the natural product K252a, inhibits MLKs in the JNK pathway with K = 17 nM [30-32]. This compound has shown neuroprotective effects in cellular and animal models [33]. CEP-1347, an orally available compound that was well tolerated in the clinic, was advanced to Phase II/III trials for assessing efficacy in Parkinson s disease. However, the clinical trial was stopped due to a lack of significant efficacy [34],... 

The enantiomers of 15, with structural similarity to the imidazole-based p38 inhibitors, have been reported to be potent inhibitors of JNK3 (ICso 3 nM) and p38 (TCso SO nM) with significant neuroprotective effects in cells [53]. 

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