N-methyl-norsalsolinol, a putative dopaminergic neurotoxin, passes through the blood-brain barrier in vivo.
In earlier studies the dihydroxylated tetrahydroisoquinoline derivatives salsolinol and 2(N)-methyl-norsalsolinol (NMNorsal), a 2(N)-analogue of salsolinol, were identified as putative endogenous neurotoxins in patients with Parkinson's disease. Since a prominent blood-brain barrier (BBB) was described to exist for salsolinol, in the present study microdialysis experiments were performed to investigate the penetration of NMNorsal through the BBB into the caudate nucleus of the rat brain. After i.p. administration of NMNorsal (20 mg/kg), it could be detected in the dialysate of the caudate nucleus with a mean maximum after 40 min. There was no alteration in extracellular dopamine or 3,4-dihydroxyphenylacetic acid levels. Addition of the monoamine oxidase inhibitor pargyline (10 microM) to the perfusate did not modify NMNorsal levels in the caudate nucleus. To corroborate the microdialysis results, homogenates of the contralateral caudate nucleus were prepared and NMNorsal could also be detected. These findings indicate that NMNorsal is indeed able to pass through the blood-brain barrier of the rat brain.
Thümen
Ansgar
A
Department of Neurology, Institute of Pharmacology and Toxicology, Medical University of Lübeck, Germany.
Behnecke
Anne
A
Qadri
Fatimunnisa
F
Bäuml
Englbert
E
Thümen
Ansgar
A
Behnecke
C Anne
CA
Qadri
Fatimunnisa
F
Bäuml
Englbert
E
Moser
Andreas
A
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D007546:Isoquinolines / Q000493:pharmacokinetics*; D008297:Male; D017551:Microdialysis; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009498:Neurotoxins / Q000493:pharmacokinetics*; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044005:Tetrahydroisoquinolines
D007546:Isoquinolines; D008996:Monoamine Oxidase Inhibitors; D009498:Neurotoxins; D044005:Tetrahydroisoquinolines; C069194:2-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline; D010293:Pargyline