Attenuation of haloperidol-induced catalepsy by noradrenaline and L-threo-DOPS.
In addition to impaired dopaminergic neurotransmission a dysfunctional noradrenergic system has been demonstrated in Parkinson's disease. L-threo-3,4-dihydroxyphenylserine (DOPS), a synthetic precursor of noradrenaline (NA), appears to be effective in the treatment of some akinetic symptoms in parkinsonian patients. In the present study the possible effect of DOPS was studied in rats, in which catalepsy was induced with haloperidol as a model for parkinsonian akinesia. Intravenous infusion of NA (1.5 and 15 micrograms/kg) or DOPS (2 and 4 mg/kg) in male Wistar rats (240-290 g) significantly decreased catalepsy. The effect of DOPS was abolished by pretreatment with the peripheral decarboxylase inhibitor benserazide (2 mg/kg). Pretreatment with Ro 40-7592, a catechol-O-methyltransferase inhibitor, potentiated and prolonged the anticataleptic effect of DOPS. The findings suggest a peripheral site of NA mediated anticataleptic action. Therapy with DOPS may be successful only without a peripheral decarboxylase inhibitor. Moreover, the therapeutic effect of DOPS may be potentiated by COMT inhibition.
Verhagen-Kamerbeek
W D
WD
Department of Neurology, University of Groningen, The Netherlands.
Hazemeijer
I
I
Korf
J
J
Lakke
J P
JP
D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001545:Benserazide / Q000494:pharmacology; D001577:Benzophenones / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced / Q000517:prevention & control*; D065098:Catechol O-Methyltransferase Inhibitors; D015103:Droxidopa / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D006220:Haloperidol / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008297:Male; D009596:Nitrophenols; D009638:Norepinephrine / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000077867:Tolcapone
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D009596:Nitrophenols; D001545:Benserazide; D000077867:Tolcapone; D006220:Haloperidol; D015103:Droxidopa; D009638:Norepinephrine