Cerebral protective agents

Kuno, A., Sugiyama, Y., Katsuta, K., Sakai, H. and Takasugi, H. (1992). Studies on cerebral protective agents. Novel 4-arylpyrimidine derivatives with anti-anoxic and anti-lipid peroxidation activities. Chem. Pharm. Bull. 40, 2423-2431. 

Meguro and co-workers used this method, among others, to prepare a variety of potential antidiabetic agents. For example, cyclization of cyclohexanecarbox-amide with ethyl 4-chloroacetoacetate gave 2-cyclohexyl-4-oxazoleacetic acid 199, albeit in poor yield (Scheme 1.54). Similarly, Ohkubo and co-workersprepared 4-(nitrophenyl)-2-phenyl-5-oxazolecarboxylic acid ethyl esters 200a and 200b as precursors to potential cerebral protective agents. 

Ginkgo biloba, which improves cerebral blood flow. Anecdotal reports of ginkgo and other potentially neuro-protective agents may be of value in the future for adjimc-tive glaucoma treatment. Lowering intraocular pressme in patients with glaucoma continues to be the primary modifiable risk fector worthy of intervention. 

Vinpocetine (2), another dmg initially categorized as a cerebral vasodilator, is a member of the vinca alkaloid family of agents (7). However, interest in this compound as a potential dmg for learning and memory deficits comes from its abiUty to act as a neuronal protectant. This compound was evaluated in 15 patients with AD over a one-year period and was ineffective in improving cognitive deficits or slowing the rate of decline (8). However, in studies of patients with chronic vascular senile cerebral dysfunction (9) and organic psycho syndrome (10), vinpocetine showed beneficial results. 

P5 Studies have shown that ebselen is an antiinflammatory and antioxidative agent. Its protective effect has been investigated in oxidative stress related diseases such as cerebral ischemia in recent years. However, experimental evidence also shows that ebselen causes cell death in several different cell types. Whether ebselen will have a beneficial or detrimental effect on cells under ischemic condition is not known. Herein, we studied the effect of ebselen... 

Through numerous studies on the mechanism of pathogenesis of cerebral ischemia, various compounds were proposed that could effectively protect the brain against ischemia. Because free radicals are one of the focuses of study in the mechanism of cerebral ischemic injury, a variety of agents that have antioxidant capacity have been developed ... 

Phillis, J.W., Clough-Helfman, C. (1990). Protection from cerebral ischemic injury in gerhils with the spin trap agent N-tert-butyl-alpha-phenylnifrone (PBN). Neurosci. Lett. 116 315-19. 

Despite the extensive effort of Feng et al. [310-331, 333-345], the mechanisms underlying the cerebro-protective actions of phthalides 30, 31 and 32 remain largely unclear. One of the possible reasons is that the authors often failed to demonstrate any causation or even correlation between the butylphthalide-mediated cerebro-protective responses and the various mechanisms proposed for example, direct evidence of protection such as reduction of infarct size was not reported in the mechanistic studies. The lack of consistency in the experimental protocols employed between the antiischemia and mechanism studies, such as 24-hour MCAO without reperfusion versus 2-hour MCAO with 24-hour reperfusion, also renders direct comparisons and correlations difficult (see Table 4). Moreover, some ambiguous data presentations and inadequate statistical analysis further complicated the interpretation of results in a number of studies. Nevertheless, these phthalides remain as potential therapeutic agents for the treatment of cerebral ischemia, and phthalide 30 was claimed to be effective for the treatment of cerebrovascular disease in a Chinese patent [7]. 

Methods - A standardized procedure for vitro susceptibility testing with 5-fluorocytoslne (Ancobon) which permitted both more accurate and more reproducible results was described.5 Two new experimental in vivo models were reported one dealt with cladosporiosls in mice treated with 5-fluoro-cytosine and the second with experimental urinary tract infections in rats caused by Candida albicans. In the former model, 5-fluorocytosine protected experimentally Infected animals against cerebral disease caused by Cladosporium tricholdes but did not clear the tissues of infection in the latter model, infections due to . albicans were treated successfully with amphotericin B, and the model appears useful in the study of anticandldal agents. 

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