Neuroprotective

Consistent with the abiUty of vinpocetine to act as an anticonvulsant is its abiUty to inhibit cellular reuptake of adenosine (15) which has been described as the brain s endogenous anticonvulsant because of its abiUty to inhibit calcium influx. Thus the property of vinpocetine to inhibit adenosine reuptake maybe responsible for the neuroprotective actions of the dmg. 

Acetylcholine Precursors. Early efforts to treat dementia using cholinomimetics focused on choline [62-49-7] (12) supplement therapy (Fig. 3). This therapy, analogous to L-dopa [59-92-7] therapy for Parkinson s disease, is based on the hypothesis that increasing the levels of choline in the brain bolsters acetylcholine (ACh) synthesis and thereby reverses deficits in cholinergic function. In addition, because choline is a precursor of phosphatidylcholine as well as ACh, its supplementation may be neuroprotective in conditions of choline deficit (104). 

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). 

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]). 

Alzheimer s disease (AD) 2. In the hippocampus of p-amylo id-treated rats, an animal model of AD, 2-AG levels are elevated and exert neuroprotection but also participate in memory retention loss 2. Inhibitors of cellular re-uptake or CB-, antagonists, possibly depending on the phase of the disorder... 

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... 

Lipton SA (2006) Paradigm shift in neuroprotection by NMDA receptor blockade memantine and beyond. Nat Rev Drug Discov 5 160-170... 

Monoamine oxidases Inhibitors Depressive illness Parkinson s disease Neuroprotection neurorescue... 

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... 

Jevtovic-Todorovic V, Todorovic SM, Mennerick S, et al Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin. Nat Med 4 460M63, 1998... 

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

Mizuno T, Kawanokuchi J, Numata K, Suzumura A (2003) Production and neuroprotective functions of fractalkine in the central nervous system. Brain Res 979(l-2) 65-70 Monteiro de Almeida S, Letendre S, Zimmerman J, Kolakowski S, Lazzaretto D, McCutchan JA, Ellis R (2006) Relationship of CSF leukocytosis to compartmentalized changes in MCP-1/ CCL2 in the CSF of HIV-infected patients undergoing interruption of antiretroviral therapy. J Neuroimmunol 179(1-2) 180-185... 

Keswani SC, Chander B et al (2003a) FK506 is neuroprotective in a model of antiretroviral toxic neuropathy. Ann Neurol 53(l) 57-64... 

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