Attenuation of haloperidol-induced catalepsy by noradrenaline and L-threo-DOPS
| Autor: | Jakob Korf, J.P.W.F. Lakke, I. Hazemeijer, W. D. J. Verhagen-Kamerbeek |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Male
Parkinson's disease STRESS REVERSAL Decarboxylase inhibitor Nitrophenols Benserazide Norepinephrine PARKINSONS-DISEASE NOREPINEPHRINE PRECURSOR Haloperidol Aromatic Amino Acid Decarboxylase Inhibitors Drug Interactions Postural Balance PARKINSONS DISEASE L-THREO-3 Chemistry General Neuroscience STRIATAL DOPAMINE Psychiatry and Mental health 4-DIHYDROXYPHENYLSERINE Neurology medicine.drug medicine.medical_specialty RO 40-7592 Catalepsy METABOLISM RAT-BRAIN Benzophenones Internal medicine NORADRENALINE medicine Animals Rats Wistar Biological Psychiatry Therapeutic effect Catechol O-Methyltransferase Inhibitors 4-DIHYDROXYPHENYLSERINE (DOPS) medicine.disease COMT INHIBITION Rats Endocrinology Droxidopa Catecholamine Neurology (clinical) Tolcapone |
| Zdroj: | Journal of neural transmission. Parkinson's disease and dementia section. 6(1) |
| ISSN: | 0936-3076 |
| Popis: | 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 mug/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. |
| Databáze: | OpenAIRE |
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