PMID- 8369108
OWN - NLM
STAT- MEDLINE
DCOM- 19931012
LR  - 20191111
VI  - 92
IP  - 2-3
DP  - 1993
TI  - Therapy with central active catechol-O-methyltransferase (COMT)-inhibitors: is 
      addition of monoamine oxidase (MAO)-inhibitors necessary to slow progress of 
      neurodegenerative disorders?
PG  - 187-95
AB  - Neurotrophic factors, like e.g. nerve growth factor (NGF), neurotrophin 3 (NT-3) 
      or brain-derived neurotrophic factor (BDNF) promote the survival and function of 
      neurones in the peripheral and central nervous system. Dopamine or other biogenic 
      amines induce the biosynthesis of neurotrophic factors in glial and neuronal 
      cells. Therefore inhibition of enzymes, like the extraneuronal and neuronal 
      located MAO or the predominantly glial situated COMT, which both metabolize 
      catecholamines, may induce an increased biosynthesis of neurotrophic factors. Due 
      to clinical studies especially MAO-B-inhibitors appear to slow the progression of 
      neurological deficits in Parkinson's disease and the cognitive decline in 
      Alzheimer's disease. On the one hand inhibition of COMT alone may also slow the 
      metabolisation of biogenic amines in glial cells and may consequently induce 
      synthesis of neurotrophic factors in glial cells. But on the other hand in vivo 
      and in vitro studies show, that COMT-inhibitors may intensify the metabolisation 
      of catecholamines in neurones by MAO, what may cause an enhanced generation of 
      free radicals. This increase of free radicals may induce lipid peroxidation of 
      membranes and therefore cause accelerated neuronal and glial cell death. For that 
      reason we conclude, that centrally active COMT-inhibitors may only be used 
      together with MAO-inhibitors in the neuroprotective treatment of 
      neurodegenerative disorders. Medical treatment with both inhibitors will have to 
      be performed very carefully due to cytotoxic effects of high catecholamine levels 
      on neuronal and glial cells and due to possible prolongation or potentiation of 
      the activity of several noradrenergic drugs in the periphery.
FAU - Muller, T
AU  - Muller T
AD  - Department of Neurology, St. Josef-Hospital, University of Bochum, Federal 
      Republic of Germany.
FAU - Kuhn, W
AU  - Kuhn W
FAU - Przuntek, H
AU  - Przuntek H
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Austria
TA  - J Neural Transm Gen Sect
JT  - Journal of neural transmission. General section
JID - 9002201
RN  - 0 (Catechol O-Methyltransferase Inhibitors)
RN  - 0 (Monoamine Oxidase Inhibitors)
SB  - IM
MH  - Animals
MH  - *Catechol O-Methyltransferase Inhibitors
MH  - Humans
MH  - Monoamine Oxidase Inhibitors/*therapeutic use
MH  - Nerve Degeneration
MH  - Nervous System Diseases/*drug therapy
RF  - 49
EDAT- 1993/01/01 00:00
MHDA- 1993/01/01 00:01
CRDT- 1993/01/01 00:00
PHST- 1993/01/01 00:00 [pubmed]
PHST- 1993/01/01 00:01 [medline]
PHST- 1993/01/01 00:00 [entrez]
AID - 10.1007/BF01244877 [doi]
PST - ppublish
SO  - J Neural Transm Gen Sect. 1993;92(2-3):187-95. doi: 10.1007/BF01244877.