Detail of "136236-51-6"

Reference

The essentiality of Bcl-2, PKC and proteasome-ubiquitin complex activations in the neuroprotective-antiapoptotic action of the anti-Parkinson drug, rasagiline

The essentiality of Bcl-2, PKC and proteasome-ubiquitin complex activations in the neuroprotective-antiapoptotic action of the anti-Parkinson drug, rasagiline. Youdim, Moussa B. H.; Amit, Tamar; Falach-Yogev, Merav; Am, Orit Bar; Maruyama, Wakkako; Naoi, Makato (Department of Pharmacology, Eve Topf and National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases Research, Technion-Faculty of Medicine, Haifa 31096, Israel). Biochemical Pharmacology, 66(8), 1635-1641 (English) 2003 Elsevier Science B.V. CODEN: BCPCA6. ISSN: 0006-2952. DOCUMENT TYPE: Journal; General Review CA Section: 1 (Pharmacology) A review. The anti-Parkinson drug, rasagiline, a irreversible propargyl possessing monoamine oxidase B inhibitor can protect neurons in vitro and in vivo from a variety of neurotoxic insults including SIN-1, glutamate, the parkinsonism inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, N-methyl-(R)-salsolinol and including beta amyloid protein. Recent studies have shown that rasagiline rapidly modulates intracellular signaling pathways involved in cell survival and death. Specifically rasagiline activates Bcl-2, Bcl-xl, protein kinase C (PKC) and reduces Bax in a variety of cells including PC-12 and neuroblastoma human dopamine derived SH-SY5Y cells. These enzymes play key roles in cellular events including modulation of apoptotic processes, neuronal plasticity and amyloid precursor protein processing. This pharmacol. action of rasagiline is also assocd. with the prevention of the neurotoxin induced fall in mitochondrial membrane potential, opening of mitochondria permeability transition pore, activation of proteasome-ubiquitin complex, inhibition of cytochrome c release and prevention of caspase 3 activation, similar to the actions of cyclosporin A or Bcl-2 over expression in SH-SY5Y cells. Rasagiline and its various derivs. induces PKC dependent release of sol. amyloid precursor protein alpha and which is blocked by inhibitors of a-secretase, PKC and MAPK-dependent signaling. Structure-activity relationship with various propargyl contg. derivs. of rasagiline including propargylamine itself has shown that the above described pharmacol. 136236-51-6 and 60267-61-0 which are cas registry numbers of substances are two of reagents here. action of these compds. resides in the propargylamine moiety. These results have provided a new understanding into the mechanism of neuroprotective actions of rasagiline and its anti-Alzheimer drug derivs. TV3326 and TV3279, which are relevant for therapy of Parkinson's disease, Alzheimer's disease and other neurodegenerative diseases. .

Pharmaceutical compositions containing L-DOPA ethyl ester

Pharmaceutical compositions containing L-DOPA ethyl ester. Cohen, Sasson; Sela, Yoram; Levy, Ruth; Shterman, Nava; Melamed, Eldad; Atlas, Daphne (Teva Pharmaceutical Industries, Ltd.; Yissum Research Development Company of the Hebrew University of Jerusalem, Israel). PCT Int. Appl. WO 9703662 A1 6 Feb 1997, 23 pp. DESIGNATED STATES: W: AL, AM, AT, AU, AZ, BB, BG, BR, BY, CA, CH, CN, CU, CZ, DE, DK, EE, ES, FI, GB, GE, HU, IL, IS, JP, KE, KG, KP, KR, KZ, LK, LR, LS, LT, LU, LV, MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT, RO, RU, SD, SE; RW: AT, BE, BF, BJ, CF, CG, CH, CI, CM, DE, DK, ES, FI, FR, GA, GB, GR, IE, IT, LU, MC, NL, PT, SE. (English). (World Intellectual Property Organization). CODEN: PIXXD2. CLASS: ICM: A61K031-165. ICS: A61K009-20. APPLICATION: WO 1996-IL58 18 Jul 1996. PRIORITY: US 1995-1368 21 Jul 1995. DOCUMENT TYPE: Patent CA Section: 63 (Pharmaceuticals) A pharmaceutical compn. contg. 136236-51-6 and 9001-66-5 are cas registry numbers of chemicals which are used as reagents here. a therapeutically effective amt. of L-dopa Et ester (I) and a carrier which comprises form 5.5 to 98.5% hydroxypropyl Me cellulose, from 0.25 to 4.5% hydroxypropyl cellulose, and from 1-90% of a carboxyvinyl polymer is disclosed. Tablets contg. 228.0 mg I provided an early burst of I followed by the maintenance of a sustained level of I over the following hours. .