Objective: Selegiline (L-deprenyl) is a selective monoamine oxidase B (MAO- B) inhibitor used in the treatment of Parkinson's disease. In addition, it is thought to rescue neurons with a loss of target-derived trophic support. Several mechanisms have been proposed to explain these phenomena, such as the production of neurotrophic actions through astrocyte activation, reduction of free radical production, or the pres ence of antiapoptotic properties. The aim of this study was to investigate whether the systemic administration of selegiline facilitates recovery after a cerebral infarction in humans. Methods: This phase II study was randomized, double-blind, and placebo con trolled. Selegiline, 5 mg, or matched placebo was given twice a day for 3 months. The drug therapy was started within 48 h after a hemispheric infarction in the territory of middle cerebral artery. There were 24 patients recruited. Twenty patients were followed up to 3 months or until their death, and they represent the efficacy analysis group. The primary efficacy parameters were Scandinavian Stroke Scale (SSS), Barthel Index (BI), and Fugl-Meyer Scale (FMS). Secondary parameters were Zung Self-Rating Depres sion Scale (ZDS) and 15-Dimensional Measure of Health Related Quality of Life test (15-D). Results: SSS improved statistically significantly from the baseline when com pared with placebo (p = 0.019). The results were parallel among the other two pri mary efficacy variables (BI and FMS), showing a positive trend for selegiline, although they did not reach statistical significance. Similarly, in the analysis of the secondary efficacy variables, both the 15-D test and ZDS supported this positive trend in favor of selegiline, although no statistically significant differences between groups were found (p = 0.06 in 15-D test). Conclusions: Selegiline seems to be beneficial after a cere bral infarction. This benefit may be due to the enhancement of the recovery process. Key Words: Cerebrovascular disorders—Stroke—Selegiline—L-deprenyl—Recovery of function.
References
1.
Nakayama H., Jorgensen HS, Raschou H., et al Recovery of upper extremity function in stroke patients the Copenhagen StrokeStudy Arch Phys Med Rehabil1994,75:394-8
2.
Feeney DMMechanisms of noradreneregic modulation of physical therapy effects on functional recovery after cortical injury In. Godstein LB, ed Advances in pharmacotherapy for recovery after strokeArmont, NY Futura, 35-78
3.
Sutton RL, Hovda DA, Feeney DMAmphetamine accelerates functional recovery following bilateral frontal cortex ablation in catBehav Neurosci1989,837-41
4.
Goldstein LBEffects of amphetamines and small related molecules on recovery after stroke in animals and manNeuropharmacology2000,39.852-9
5.
Walker-Batson D., Smith P., Curtis S., et al. Amphetamine paired with physical therapy accelerates motor recovery after stroke. further evidenceStroke1995;26:2254-9
6.
Oerthel WH, Quinn NPParkinson's disease. drug therapyBail-heres Clin Neurol1997,6.89-108
7.
Magyar KB, Szende J., Lengyel J., et al The neuroprotective and neuronal rescue effects of (-)-deprenyl . J Neural Transm1998, 52(suppl) 109-23
8.
Tatton WGSelegiline can mediate neuronal rescue rather than neuronal protectionMov Disord1993,8(suppl) S20-30
9.
Knollema S., Aukema W., Hom H., et al L-deprenyl reduces brain damage in rats exposed to transient hypoxia-ischemiaStroke1995,26.1883-7
Lahtinen J. , Koistmaho J., Kauppinen R., et al Selegiline treatment after transient global ischemia in gerbils enhances the survival of CA1 pyramidal cells in the hippocampusBrain Res1997;757260-7.
12.
Paterson IA , Barber AJ, Gelowitz DL, et al Deprenyl reduces delayed neuronal death of hippocampal pyramidal cells. Neurosci Biobehav Rev1997;21181-6.
13.
Semkova I., Wolz P., Schilling M., et al. Selegiline enhances NGF synthesis and protects central nervous system neurons from excitotoxic and ischemic damageEur J Pharmacol1996,315.19-30
14.
Biagini G., Frasoldati A., Fuxe K., et al. The concept of astrocyte-kinetic drug in the treatment of neurodegenerative diseases evidence for L-deprenyl-induced activation of reactive astrocytesNeurochem Int1994,25:17-22.
15.
Riva MA, Molteni R., Racgni G.L-deprenyl potentiates cAMPmduced of FGF-2 mRNA levels in rat cortical astrocytesNeuroreport1997,8.2165-8
16.
Tang YP, Ma YL, Chao CC, et al Enhanced glial cell line-derived neurotrophic factor mRNA expression upon (-)-deprenyl and melatonin treatmentsJ Neurosci Res1998;53593-604
17.
Lessman V.Neurotrophin-dependent modulation of glutamatergic synaptic transmission in the mammalian CNSGen Pharmacol1998,31:667-74
18.
Schuman EMNeurotrophin regulation of synaptic transmissionCurr Opin Neurobiol1999;9:105-9.
Caleo M., Lodovichi C., Maffei L.Effects of nerve growth factor on visual cortical plasticity require afferent electrical activity. Eur J Neurosci1999,112979-84
21.
Kuhmonen J. , Jolkkonen J., Haapalmna A., et al The neuroprotective effects of deprenyl m the gerbil hippocampus following transient global ischemiaJ Neural Transm2000,107779-86
22.
Scandinavian Stroke Study GroupMulticenter trial of hemodilution m ischemic stroke. background and study protocolStroke1985,16.885-90
23.
Scandinavian Stroke Study GroupMulticenter trial of hemodilution m ischemic strokeStroke1987,18.691-9
24.
Shah S., Vanclay F., Cooper D.Improving the sensitivity of the Barthel index for stroke rehabilitationJ Clin Epidemiol1989,42703-9
25.
Lindenstrøm E., Boysen G., Christiansen LW, et al. Reliability of Scandinavian Neurological Stroke Scale. Cerebrovasc Dis1991,1. 103-7
Fugl-Meyer A., Jaasko L.Leyman I.The post stroke hemiplegic patient a method of evaluation of physical performance. Scand Rehabil Med1975,713-31.
28.
Sintonen H. , Pekurinen M.15D-askel kohti yleista terveyteen liittyvan elamanlaadun mittaria Sos laaketieteenAikakauslehti1989,2685-95
29.
Zung WwkA self rating depression scaleArch Gen Psychiatry1965,12.63-70.
30.
Grade C., Redford B., Chrostowski J., et al Methylphenidate in early poststroke recovery: a double-blind, placebo-controlled studyArch Phys Med Rehabil1998,791047-50
31.
Biel JH, Bopp BAAmphetamines structure-activity relationships In Iverson L, Synder S, eds Handbook of psychopharmacology. Vol II New YorkPlenum Press, 1979.131.
32.
del Zoppo GJ , Wagner S., Tagaya M.Trends and future developments m the pharmacological treatment of acute ischemic stroke. Drugs1997,54.9-38
33.
Christou I. , Alexandrov AV, Burgm WS, et al. Timing of recanalization after tissue plasminogen activator therapy determined by transcranial doppler correlates with clinical recovery from ischemic strokeStroke2000;311812-6.
34.
Puurunen K. , Jolkkonen J., Sirvio J., et al Selegiline combined with enriched-environment housing attenuates spatial learning deficits following focal cerebral ischemia in ratsExp Neurol2001,167348-55
35.
Feeney DM, Gonzales A., Law WAAmphetamine, halopendol, and experience interact to affect rate of recovery after motor cortex injuryScience1982,217855-7
36.
Feeney DM, Hovda DAReinstatement of binocular depth perception by amphetamine and visual experience after visual cortex ablationBrain Res1985 ,342.352-6
37.
Puurunen K. , Jolkkonen J., Sirvio J., et al An α2-adrenergic antagonist, atipamezole, facilitates behavioral recovery after focal cerebral ischemia m ratsNeuropharmacology2001;40:597-606
