TY - JOUR
T1 - Pharmacological aspects of the neuroprotective effects of irreversible MAO-B inhibitors, selegiline and rasagiline, in Parkinson’s disease
AU - Szökő, Éva
AU - Tábi, Tamás
AU - Riederer, Peter
AU - Vécsei, László
AU - Magyar, Kálmán
PY - 2018/11/1
Y1 - 2018/11/1
N2 - The era of MAO-B inhibitors dates back more than 50 years. It began with Kálmán Magyar’s outstanding discovery of the selective inhibitor, selegiline. This compound is still regarded as the gold standard of MAO-B inhibition, although newer drugs have also been introduced to the field. It was revealed early on that selective, even irreversible inhibition of MAO-B is free from the severe side effect of the non-selective MAO inhibitors, the potentiation of tyramine, resulting in the so-called ‘cheese effect’. Since MAO-B is involved mainly in the degradation of dopamine, the inhibitors lack any antidepressant effect; however, they became first-line medications for the therapy of Parkinson’s disease based on their dopamine-sparing activity. Extensive studies with selegiline indicated its complex pharmacological activity profile with MAO-B-independent mechanisms involved. Some of these beneficial effects, such as neuroprotective and antiapoptotic properties, were connected to its propargylamine structure. The second MAO-B inhibitor approved for the treatment of Parkinson’s disease, rasagiline also possesses this structural element and shows similar pharmacological characteristics. The preclinical studies performed with selegiline and rasagiline are summarized in this review.
AB - The era of MAO-B inhibitors dates back more than 50 years. It began with Kálmán Magyar’s outstanding discovery of the selective inhibitor, selegiline. This compound is still regarded as the gold standard of MAO-B inhibition, although newer drugs have also been introduced to the field. It was revealed early on that selective, even irreversible inhibition of MAO-B is free from the severe side effect of the non-selective MAO inhibitors, the potentiation of tyramine, resulting in the so-called ‘cheese effect’. Since MAO-B is involved mainly in the degradation of dopamine, the inhibitors lack any antidepressant effect; however, they became first-line medications for the therapy of Parkinson’s disease based on their dopamine-sparing activity. Extensive studies with selegiline indicated its complex pharmacological activity profile with MAO-B-independent mechanisms involved. Some of these beneficial effects, such as neuroprotective and antiapoptotic properties, were connected to its propargylamine structure. The second MAO-B inhibitor approved for the treatment of Parkinson’s disease, rasagiline also possesses this structural element and shows similar pharmacological characteristics. The preclinical studies performed with selegiline and rasagiline are summarized in this review.
KW - MAO-B inhibition
KW - Neuroprotection
KW - Rasagiline
KW - Selegiline
U2 - 10.1007/s00702-018-1853-9
DO - 10.1007/s00702-018-1853-9
M3 - Journal article
C2 - 29417334
AN - SCOPUS:85041522557
SN - 0300-9564
VL - 125
SP - 1735
EP - 1749
JO - Journal of Neural Transmission
JF - Journal of Neural Transmission
IS - 11
ER -