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Progress and Prospects in Parkinson's Research/Therapy/Neuroprotection/Rasagiline

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Rasagiline is a rare example of a neuroprotective therapy which has made its way through the entire testing regime and is now widely prescribed.


Background

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Rasagiline - Trading names Azilect and AGN 113 is an irreversible inhibitor of the enzyme monoamine oxidase MAO-B.

Research

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1985

Heikkila et al [1] found that rasagiline reduced dopamine toxicity in MPTP-induced rats and mice.


1999

Huang et al [2] assesed the ability of rasagiline to speed up recovery from brain injury (in mice).

Early administration of rasagiline or TVP1022 can reduce the immediate sequelae of brain injury

Speiser et al [3] confirmed the neuroprotective effects of rasagiline in rats.

2000

Mruyama et al [4] proved that rasagiline prevented cell death.


2001

Youdim et al [5] conducted a comparison of the benefits of rasagiline and selegiline. They concluded:-

Rasagiline was three to 15 times more potent than selegiline for inhibition of MAO-B in rat brain and liver in vivo on acute and chronic administration, but had similar potency in vitro. 6. These data together with lack of tyramine sympathomimetic potentiation by rasagiline, at selective MAO-B inhibitory dosage, indicate that this inhibitor like selegiline may be a useful agent in the treatment of Parkinson's disease in either symptomatic or L-DOPA adjunct therapy, but lack of amphetamine-like metabolites could present a therapeutic advantage for rasagiline.

Murer et al [6] found that rasagiline improved the release of Brain-derived neurotrophic factor (BDNF)


2004

Blandini et al [7] Rats were render Parkinsonian by 8-OHDA injections and were then treated daily for 6 weeks with rasagiline. It was found that there was a marked increase in the survival of dopaminergic neurons in the lesioned substantia nigra, compared to controls.


2009

Hauser et al [8] The purpose of this study was to compare the long-term clinical outcome of early versus delayed rasagiline treatment in early Parkinson's disease.

Compared to delayed start, early initiation of rasagiline provided long-term clinical benefit, even in the face of treatment with other dopaminergic agents.


2011

Olanow et al [9] A total of 1176 subjects with untreated Parkinson's disease were randomly assigned to receive rasagiline (at a dose of either 1 mg or 2 mg per day) for 72 weeks (the early-start group) or placebo for 36 weeks followed by rasagiline (at a dose of either 1 mg or 2 mg per day) for 36 weeks.

Early treatment with rasagiline at a dose of 1 mg per day provided benefits that were consistent with a possible disease-modifying effect, but early treatment with rasagiline at a dose of 2 mg per day did not. Because the two doses were associated with different outcomes, the study results must be interpreted with caution.

Rascol et al [10] 1176 patients with untreated early Parkinson's disease were randomly assigned to receive rasagiline 1 mg or 2 mg per day for 72 weeks (early-start groups) or placebo for 36 weeks followed by rasagiline 1 mg or 2 mg per day for 36 weeks (delayed-start groups). The findings showed that rasagiline delayed the need for symptomatic antiparkinsonian drugs.

2013

Kaur et al [11] reported the case of a 58 year old woman with PD, who was treated with a mixture of rasagiline and the anti-depressant drugs venlafaxine and buproprion. The three drugs appeared to act in combination to bring about a significant improvement in her condition.

Further Reading

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2008

Nayak, Lakhmi and Henchcliffe, Claire. Full Text Neuropsychiatr. Dis. Treat. 4(1): 23–32.

Rasagiline in treatment of Parkinson’s disease.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2515917/?tool=pmcentrez

2009

Malaty, Irene A. and Fernandez, Hubert H. Full Text Ther. Clin. Risk Manag. 5: 413–419.

Role of rasagiline in treating Parkinson’s disease: Effect on disease progression.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695242/?tool=pmcentrez


2010

Ahlskog, J. Eric and Utti, Ryan J, Full Text Neurology. 74(14): 1143–1148.

Rasagiline, Parkinson neuroprotection, and delayed-start trials. Still no satisfaction?

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2865777/?tool=pmcentrez


Leegwater-Kim, Julie and Bortan, Elena Full Text Clin. Interv. Aging. 5: 149–156.

The role of rasagiline in the treatment of Parkinson’s disease.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877525/?tool=pmcentrez

Today

Use the following links to query the PubMed, PubMed Central and Google Scholar databases using the Search terms:- Parkinson's_Disease Rasagiline.

This will list the latest papers on this topic. You are invited to update this page to reflect such recent results, pointing out their significance.

Pubmed (abstracts)

Pubmed_Central (Full_Text)

Google_Scholar

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Therapy > Neuroprotection

Sub Pages:

Neuroprotective agents
Substances with possible neuroprotective properties:
Caffeine,--Celastrol,--Co-Enzyme Q10,--Creatine,--DHA,--Exendin-4 (EX-4),--GDNF,--Glutathione (GSH),--GM1,--Isradipine,--Melatonin,--Minocycline,--Nicotine,--NSAIDs,--Phenylbutyrate,--Phytic Acid,--Probucol,--Quinoxaline,--Rasagiline,--Riboflavin,--Statins,--Tolcapone,--Urate & Uric Acid,--Vitamin D,--Vitamin E,--

References

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  1. ↑ Heikkila R,E.; Manzino, L.; Cabbat, F. S.; Duvoisin, R. C. (1985) Abstract J. Neurochem. 45 (4):1049 - 1054. Studies on the oxidation of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine by monoamine oxidase B. http://www.ncbi.nlm.nih.gov/pubmed/3928814
  2. ↑ Huang, W.; Chen, Y.; Shohami. E.; Weinstock, M.(1999) Abstract Eur. J. Pharmacol. 366 (2-3):127-135. Neuroprotective effect of rasagiline, a selective monoamine oxidase-B inhibitor, against closed head injury in the mouse. http://www.ncbi.nlm.nih.gov/pubmed/10082192
  3. ↑ Speiser, Z.; Mayk, A. Eliash, S. and Cohen, S. (1999) Abstract J. Neural Transm. 106 (7-8):593-606. Studies with rasagiline, a MAO-B inhibitor, in experimental focal ischemia in the rat. http://www.ncbi.nlm.nih.gov/pubmed/10907720
  4. ↑ Maruyama W,; Akao, Y.; Youdim, M. B. and Naoi, M.(2000) Abstract J Neural. Transm. Suppl. (60):171-186. Neurotoxins induce apoptosis in dopamine neurons: protection by N-propargylamine-1(R)- and (S)-aminoindan, rasagiline and TV1022. http://www.ncbi.nlm.nih.gov/pubmed/11205138
  5. ↑ Youdim, M. B.; Gross, A. and Finberg, J. P. (2001) Abstract Br. J. Pharmacol. Jan;132 (2):500-506. Rasagiline [N-propargyl-1R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase B. http://www.ncbi.nlm.nih.gov/pubmed/11159700
  6. ↑ Murer, M. G.; Yan, Q. and Raisman-Vozari, R. (2001) Abstract Prog. Neurobiol. 63 (1):71-124. Brain-derived neurotrophic factor in the control human brain, and in Alzheimer's disease and Parkinson's disease. http://www.ncbi.nlm.nih.gov/pubmed/11040419
  7. ↑ Blandini, F.; Armentero, M, T.; Fancellu, R.; Blaugrund, E. and Nappi, G. (2004) Abstract Exp. Neurol. 187(2):455 - 459. Neuroprotective effect of rasagiline in a rodent model of Parkinson's disease. http://www.ncbi.nlm.nih.gov/pubmed/15144871
  8. ↑ Hauser, R. A.; Lew, M. F.; Hurtig, HI.; Ondo, WG.; Wojcieszek, J.; Fitzer-Attas, C.J. and TEMPO Open-label Study Group. (2009) Abstract Mov. Disord. 24 (4):564-573. Long-term outcome of early versus delayed rasagiline treatment in early Parkinson's disease. http://www.ncbi.nlm.nih.gov/pubmed/19086083
  9. ↑ Olanow, C. W.; Rascol, O,; Hauser, R,; Feigin, P. D.; Jankovic, J.; Lang, A.; Langston, W.; Melamed, E.; Poewe, W.; Stocchi, F.; Tolosa, E. and ADAGIO Study Investigators. (2011) Abstract N. Engl. J. Med. 364 (19):1882. A double-blind, delayed-start trial of rasagiline in Parkinson's disease.http://www.ncbi.nlm.nih.gov/pubmed/19776408
  10. ↑ Rascol, O.; Fitzer-Attas, C. J.; Hauser, R.; Jankovic, J.; Lang A,; Langston, J. W.;Melamed, E.; Poewe, W.; Stocchi, F.; Tolosa, E.; Eyal E.; Weiss, Y. M. and Olanow; C. W. (2011) Abstract Lancet Neurol. 10 (5):415-423. A double-blind, delayed-start trial of rasagiline in Parkinson's disease (the ADAGIO study): prespecified and post-hoc analyses of the need for additional therapies, changes in UPDRS scores, and non-motor outcomes. http://www.ncbi.nlm.nih.gov/pubmed/21482191
  11. ↑ Kaur, N.; Madan, R. and Sharma A. (2013) Abstract Innov. Clin. Neurosci. )11-12) 39-41 Successful use of rasagiline in combination with two antidepressants: a case report. http://www.ncbi.nlm.nih.gov/pubmed/23346517
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