Neuroprotective compounds

Crobenetine, a neuroprotectant compound, induces anti-hyperalgesia in an animal model for chronic inflammatory pain... 

Lockhart BP, Lestage PJ (2003) Cognition enhancing or neuroprotective compounds for the treatment of cognitive disorders why when which Exp Gerontol 38 119-128... 

Conforti P, Ramos C, Apostol BL, Simmons DA, Nguyen HP, Riess O, Thompson LM, Zuccato C, Cattaneo E (2008) Blood level of brain-derived neurotrophic factor mRNA is progressively reduced in rodent models of Huntington s disease restoration by the neuroprotective compound CEP-1347. Mol CeU NeuiDsd 39 1-7... 

Badaria, F.A., Guirguis, A.N., Perovic, S., Steffen, R., Muller, W.F.G., and Schroder, H.C. (1998) Sarcophytolide a new neuroprotective compound from the soft coral Sarcophyton glaucum. Toxicology, 131, 133-143. 

A large number of molecules have provided experimental evidence of neuroprotection in in vitro and in vivo models of Parkinson s disease and many of these putative neuroprotective substances are now the objects of clinical trials. Recently, a team of experts has identified potential neuroprotective agents to be tested in pilot studies [4]. Twelve compounds have been considered for clinical trials caffeine, coenzyme Q 10, creatine, estrogen, GPI1485, GM-1 ganglioside, minocycline, nicotine, pramipexole, ropinirol, rasagiline, and selegiline (for individual discussion see [4]). 

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... 

An important class of noncompetitive antagonists selective for AMPA receptors is represented by the 2,3-benzodiazepines such as GYKI 53655. These compounds act at sites different from those acted on by cyclothiazide and are useful tools for isolating synaptic responses mediated by kainate receptors. These compounds also show some promise as neuroprotective drugs for treating ischemic neuronal injury. 

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],... 

SP-600125 was one of the first JNK inhibitors to be reported with potent JNK 1, 2 and 3 inhibitory activity (IC50 = 40,40 and 90 nM, respectively) [37], This tool compound has been studied extensively in a variety of cellular and animal models of inflammation and neuroprotection, among others. The profile of SP-600125 has been discussed in a number of reviews [6,28,29] and will not be discussed here. 

At this time, however, we are not aware of any compounds selected primarily by their neuroprotection activity on rodent models that have established clinical efficacy for dementias or related neurodegenerative diseases. This may be partially explained by their priority development for stroke, and clinicians have found it is difficult or unlikely to slow the ischemia in patients if they are not treated aggressively within 3 h of the initial ischemic event. The speed of neurodegeneration in stroke (cerebral ischemia) makes it a much more difficult target for drug intervention than neurodegeneration from slower pathologies such as Alzheimer s, Parkinson s, and malfunctions in neurotransmitters. 

NT037 Castagnoli, K. P., S. J. Steyn, J. P. Petzer, C. J. Van der Schyf, and N. Castagnoli Jr. Neuroprotection in the MPTP Parkinsonian C57BL/6 mouse model by a compound isolated from tobacco. Chem Res Toxicol 2001 14(5) 523-527. 

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