Neuroprotective agent

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]). 

Kemp JA, Kew JNC, Gill R (1999) NMDA receptor antagonists and their potential as neuroprotective agents, chapter 16 Ionotropic glutamate receptors in the CNS. Springer Verlag... 

Several glutamate antagonists have been or are in the process of being evaluated both preclinically and clinically as neuroprotective agents. For example, MK-801, an NMDA antagonist, reduces the detrimental effects of excess glutamate (as well as other insults to neurons) in a variety of animal models. Unfortunately the... 

In noncancer-related pharmacology, GSK3 is inhibited by lithium at therapeutic concentrations, implying that the long-established effectiveness of lithium in the treatment of psychiatric mood disorders (and more recently as a neuroprotective agent) may be linked to GSK3 inhibition. Antipsychotics such as haloperidol... 

Pharmacologic neuroprotection, which might be expected to prevent tissue necrosis or apoptosis until tissue reperfusion can be achieved with rt-PA, is a theoretically attractive adjunct to rt-PA treatment. Despite positive studies in animals, all evaluations of neuroprotective agents in humans have failed. Most recently, the promising initial results for intravenous NXY-059, a ffee-radical-trapping agent, were not replicated in a confirmatory phase III trial (unpublished data). 

New glutamate and aspartate analogues as potential neuroprotective agents. J. Med. Chem. 2001, 44, 2507-2510. 

Pyridylstannanes have been cross-coupled with numerous aryl- and heteroaryl halides as well as various other electrophiles. For example, an extension of Stille s original methodology to 3-trimethylstannylpyridine and acid chloride 73 gave the corresponding ketone 74, which was then converted to 2S-(+)-nicotinylalanine 75, a neuroprotection agent [62],... 

Brewster ME, Pop E, Foltz RL, Reuschel S, Griffith W, Amselem S, Biegon A. (1997). Clinical pharmacokinetics of escalating i.v. doses of dexanabinol (HU211), a neuroprotectant agent, in normal volunteers. IntJ Clin Pharmacol Ther. 35 9361-65. 

Gill R, Kemp JA, Richards JG, Kew JNC (1999) NMDA receptor antagonists past disappointments and future prospects as neuroprotective agents. Curr Opin Cardiovasc Pulm Ren Invest Drugs 1 576-591... 

Antagonists for any of the various modulatory sites around the NMDA—calcium channel complex would possibly restrict the flow of calcium and close the channel and therefore be candidates for neuroprotective agents. Such antagonists are being... 

We have already briefly mentioned the mechanism of action of PCP in Chapter 10 in our discussion on neuroprotective agents (Fig. 10—24). It acts as an allosteric modulator of the NMDA subtype of glutamate receptor (Figs. 13—12 and 13—13). It specifically acts to block this receptor and to decrease the flux of calcium into the cell. Phenylcyclidine itself and other agents that act at the PCP receptor may be neuroprotective, but apparently only at the expense of disrupting memory and causing psychosis (Fig. 13—13). 

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