A Selegiline

The neuroprotection of SH-SY54 cells from apoptosis caused by NOR-4 and SIN-1 is not related to inhibition of MAO-B, because SH-SY54 contains only MAO-A. Selegiline is able to protect dopaminergic neurons from the toxicity of MPTP and also of MPP an oxidized product of MPTP by MAO-B. This indicates that the neuroprotection by selegiline does not require blockage of the conversion of MPTP to MPP+. 

Barrett JS, Hochadel TJ, Morales RJ, Rdial S, DeWitt KE, Wats i SK, Damow J, Azzaro AJ, DiSanto AR. Presscr response to tyramine after sir le 24-hour a f>lication of a selegiline transdermal system in healthy m Ae. JClmPh umacol( 99T) 37,238-47. 

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]). 

Acute treatment with nonselective MAO inhibitors (iproniazid, tranylcypromine, phenelzine), as a consequence of inhibiting both forms of the enzyme, increase, brain levels of all monoamines (phenylethylamine, tryptamine, methylhistamine aminergic neurotransmitters (dopamine, noradr enaline, adrenaline and serotonin). By contrast MAO-A inhibitors (clorgyline) increase serotonin and noradrenaline, while MAO-B inhibitors (selegiline, rasagiline) increase brain levels... 

Sano M, Ernesto C, Thomas RG et al (1997) A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer s disease. The Alzheimer s Disease Cooperative Study. N Engl JMed 336 1216-1222... 

More than 40 medications have been investigated but none have shown consistent efficacy for primary cocaine or amphetamine dependence. These medications include dopaminergic agonists, antidepressants, and more recently disulfiram, selegiline, and a cocaine vaccine (see Table 5—2 for summary). Studies have been relatively brief and have focused on abstinence initiation rather than on relapse prevention, but even these modest treatment goals have not been attained. The focus in the discussion that follows is on pharmacotherapies for cocaine dependence, because very few clinical trials have been completed with amphetamine-dependent patients. Furthermore, none of the studies of amphetamine dependence have shown results different from those described for cocaine dependence (Rawson et al. 2002b Srisurapanont et al. 2001). 

Monoamine oxidase exists in two forms, MAOa and MAOb. The former is more active against NA and 5-HT than it is against DA, which is a substrate for both, even though, like S-phenylethylamine, it is more affected by MAOb. H seems likely that MAOb is the dominant enzyme in human brain and inhibitors of it, such as selegiline, have some value in the treatment of Parkinson s disease by prolonging the action of the remaining endogenous DA as well as that formed from administered levodopa. 

There have been few attempts to manipulate the monoamines in AzD and those using selegiline, the MOAb inhibitor, have shown little effect although the 5-HT3 antagonist, ondansetron, may give a slight improvement. 

Yavich, L, Sirvio, J, Haapalinna, A, Puumala, T, Koivisto, E, Heinonen, E and Reikkinen, PJ (1996) The systemic administration of tacrine or selegiline facilitate spatial learning in aged Fisher 344 rats. J. Neural Trans. 103 619-626. 

Selegiline A selective MAO-B inhibitor, also called L-deprenyl, used in the treatment of Parkinson s disease. 

---