Biomedical subjects

P Jenner

Publications and source records attributed to P Jenner.

At least 181 records · Page 10Linked to original sources

PubMed1994

Nigral dopaminergic cell loss in vitamin E deficient rats.

alpha-Tocopherol concentrations in brain were reduced to 3% of control levels in rats fed a vitamin E deficient diet for 52 weeks. Vitamin E deficiency resulted in a 19-33% loss of tyrosine hydroxylase (TH) immunopositive neurones in the substantia nigra, but not in the adjacent ventral tegmental area, compared with controls. Vitamin E deficiency, however, did not reduce striatal dopamine concentrations or turnover. When antioxidant defence mechanisms are defective, as in chronic vitamin E deficiency, the nigrostriatal pathway may be affected by oxidative damage and this may have implications for Parkinson's disease.

Animals↗

PubMed1994

Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting basal ganglia.

Reduced glutathione (GSH) and oxidized glutathione (GSSG) levels were measured in various brain areas (substantia nigra, putamen, caudate nucleus, globus pallidus, and cerebral cortex) from patients dying with Parkinson's disease, progressive supranuclear palsy, multiple-system atrophy, and Huntington's disease and from control subjects with no neuropathological changes in substantia nigra. GSH levels were reduced in substantia nigra in Parkinson's disease patients (40% compared to control subjects) and GSSG levels were marginally (29%) but insignificantly elevated; there were no changes in other brain areas. The only significant change in multiple-system atrophy was an increase of GSH (196%) coupled with a reduction of GSSG (60%) in the globus pallidus. The only change in progressive supranuclear palsy was a reduced level of GSH in the caudate nucleus (51%). The only change in Huntington's disease was a reduction of GSSG in the caudate nucleus (50%). Despite profound nigral cell loss in the substantia nigra in Parkinson's disease, multiple-system atrophy, and progressive supranuclear palsy, the level of GSH in the substantia nigra was significantly reduced only in Parkinson's disease. This suggests that the change in GSH in Parkinson's disease is not solely due to nigral cell death, or entirely explained by drug therapy, for multiple-system atrophy patients were also treated with levodopa. The altered GSH/GSSG ratio in the substantia nigra in Parkinson's disease is consistent with the concept of oxidative stress as a major component in the pathogenesis of nigral cell death in Parkinson's disease.

Aged↗

PubMed1994

Glutathione-related enzymes in brain in Parkinson's disease.

The activities of enzymes related to glutathione synthesis, degradation, and function were analyzed in various brain regions (cerebral cortex, caudate nucleus, putamen, globus pallidus, and substantia nigra) from patients dying with pathologically proven Parkinson's disease (PD) and multiple system atrophy (MSA), and from matched controls with no neurological disorder. The activity of the glutathione degradative enzyme, gamma-glutamyltranspeptidase, was selectively elevated in substantia nigra (SN) in PD. In contrast, the activity of the synthetic enzyme, gamma-glutamylcysteine synthetase, was unaltered in SN and other brain areas in PD. Similarly, glutathione peroxidase and glutathione transferase activities were unaltered in SN or in other brain regions in PD. gamma-Glutamylcysteine synthetase, gamma-glutamyltranspeptidase, glutathione peroxidase, and glutathione transferase activities were normal in SN and most other brain areas in MSA. However, glutathione peroxidase activity was increased in the lateral globus pallidus and caudate nucleus in MSA. The depletion of reduced glutathione (GSH) in the SN in PD, with no change in oxidized glutathione (GSSG), may be due to efflux of GSH mainly out of glia promoted by gamma-glutamyltranspeptidase, perhaps with additional increased conversion of GSH to GSSG (which itself is transported out of cells by gamma-glutamyltranspeptidase), in response to increased hydrogen peroxide formation.

Aged↗

PubMed1994

Complex I, iron, and ferritin in Parkinson's disease substantia nigra.

Elevated iron levels, enhanced oxidative damage, and complex I deficiency have been identified in the substantia nigra of Parkinson's disease patients. To understand the interrelationship of these abnormalities, we analyzed iron levels, ferritin levels, and complex I activity in the substantia nigra of patients with Parkinson's disease. Total iron levels were increased significantly, ferritin levels were unchanged, and complex I activities were decreased significantly in the substantia nigra samples. The failure of ferritin levels to increase with elevated iron concentrations suggests that the amount of reactive iron may increase in the substantia nigra of Parkinson's disease patients. There was no correlation between the iron levels and complex I activity or the iron-ferritin ratio and complex I activity in the substantia nigra samples.

Aged↗

PubMed1994

Increased levels of lipid hydroperoxides in the parkinsonian substantia nigra: an HPLC and ESR study.

Previous studies examining the involvement of oxidative stress in the substantia nigra in Parkinson's disease have measured terminal products of lipid peroxidation or the function of antioxidant defense systems. We report a more specific early marker of lipid peroxidation, lipid hydroperoxides, in a high-performance liquid chromatography (HPLC) and electron spin resonance (ESR) investigation. HPLC-chemiluminescent detection revealed two classes of lipid hydroperoxides in brain tissue extracts--free fatty acid hydroperoxides and cholesterol lipid hydroperoxides. Only cholesterol lipid hydroperoxides were consistently detected in all tissue extracts. Cholesterol lipid hydroperoxides had a 10-fold increase in the Parkinson's disease substantia nigra compared to control subjects. ESR detection of radical degradation products, including those of lipid hydroperoxides, in nigral homogenates incubated with the spin trap N-t-butyl-alpha-phenyl nitrone (PBN) showed a marked variation in ESR signal between tissues. Despite the increased levels of lipid hydroperoxides in parkinsonian substantia nigra, there was no overall difference in ESR signal intensity between nigral tissues from controls and from patients with Parkinson's disease. The increased levels of an early component of the peroxidation chain in substantia nigra in Parkinson's disease support the hypothesis of a continuous toxic process involving oxygen radical activity. However, using previously frozen tissue, ESR evidence for increased radical formation could not be demonstrated.

Chromatography, High Pressure Liquid↗

PubMed1994

Chronic administration does not alter the accumulation of L-dopa into muscle.

Rats were treated for 12 months with L-dopa (191.4-210.4 mg/kg/day) plus carbidopa (23.9-26.2 mg/kg/day), or carbidopa (24.4-26.3 mg/kg/day) alone. Four days after drug withdrawal, animals received an acute challenge with either L-dopa (50 mg/kg p.o.) alone or following acute carbidopa (25 mg/kg i.p.) pretreatment, and the uptake and metabolism of L-dopa in muscle was studied. Following the acute bolus challenge, plasma levels of L-dopa peaked between 0.5 and 3 h after L-dopa alone and between 1.5 and 2 h after L-dopa plus carbidopa. Peak levels in muscle were observed between 1.5 and 4 h after L-dopa administration, and this accumulation was enhanced by the acute pretreatment with carbidopa. Chronic administration of L-dopa plus carbidopa or carbidopa alone for 12 months had no effect on the accumulation of L-dopa into muscle following the acute challenge with L-dopa alone or after carbidopa pretreatment. 3-O-Methyldopa, dopamine, DOPAC, and HVA levels were elevated in both plasma and muscle following acute oral challenge with L-dopa or L-dopa plus carbidopa. Levels of these metabolites were unaffected by chronic administration of L-dopa plus carbidopa or carbidopa alone. In conclusion, chronic administration of L-dopa plus carbidopa did not alter the accumulation of L-dopa into muscle following an acute oral challenge with the drug, with or without carbidopa pretreatment.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

An autoradiographic study of the differential effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on striatal and extrastriatal D-1 and D-2 dopamine receptors in the rat.

The effect of in vivo administration of the alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on striatal and extrastriatal D-1 and D-2 dopamine (DA) receptors was investigated in the rat. N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline treatment reduced specific [3H]SCH 23390 (7-chloro-8-hydroxy-2,3,4,5-tetrahydro-3-methyl-1-phenyl-1H-3-benzaze pin e) binding to D-1 DA receptors in the striatum (42-46% of saline-treated controls), entopeduncular nucleus (20%) and substantia nigra pars reticulata (23%). Similarly, specific [3H]spiperone binding to D-2 DA receptors was decreased in the striatum (28-37% of saline-treated controls). However, [3H]spiperone binding in the substantia nigra pars compacta (67%) was much less affected. In vivo pretreatment with the D-1 DA antagonist SCH 23390 selectively and dose dependently protected [3H]SCH 23390 binding against the effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline in the striatal/extrastriatal regions. Pretreatment with the D-2 DA antagonist raclopride or the D-2 DA agonist quinpirole selectively protected [3H]spiperone binding. In contrast, pretreatment with the D-1 DA agonist SKF 38393 (7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) not only protected [3H]-SCH 23390 binding but at very high doses protected striatal [3H]spiperone binding. The differential alkylating effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline on striatal vs extrastriatal D-1 and D-2 DA receptors may be related to their post- (striatal DA receptors) and pre-synaptic (extrastriatal DA receptors) localizations, respectively. The present results further demonstrate that in vivo, SCH 23390 and raclopride/quinpirole retain their D-1 and D-2 DA receptor selectivity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1994

Neurotensin, substance P, delta and mu opioid receptors are decreased in basal ganglia of Parkinson's disease patients.

The specific binding of [3H]neurotensin, [3H]substance P, [3H]D-Ala2-D-Leu5-enkephalin (delta receptors) and [3H]-Tyr-D-Ala-Gly-(NMe)Phe-Gly-ol (mu receptors) were studied in membrane preparations of caudate nucleus, putamen, globus pallidus and substantia nigra from patients with Parkinson's disease and from age-matched controls. The density of neurotensin receptors was decreased in globus pallidus (lateral and medial segments) in parkinsonian brain. Substance P receptors were reduced in the putamen (anterior and posterior) and in lateral globus pallidus in Parkinson's disease. There was a reduction in the density of opioid receptors in posterior putamen and in mu receptors in caudate nucleus and putamen (anterior and posterior). No differences in neuropeptide receptor binding were observed in substantia nigra from parkinsonian brains compared with control subjects. The reductions in neuropeptide receptor density were less marked than the decrease in caudate and putamen content of dopamine and its metabolites. This suggests that neuropeptide receptors are only partially localized to striatal dopamine terminals.

Adult↗

PubMed1994

Plasma HVA levels following debrisoquine administration do not reflect cerebral dopamine loss in early Parkinson's disease.

Plasma levels of homovanillic acid (pHVA) following debrisoquine (DBQ) administration may be indicative of central dopaminergic activity. The effect of DBQ (10-20 mg) administration on pHVA in young healthy volunteers was studied to establish a protocol for use in de novo patients with Parkinson's disease. Subsequently, pHVA in de novo patients with Parkinson's disease were measured and compared to young healthy volunteers. Following DBQ (10 mg) administration to healthy volunteers, pHVA fell with time to a maximum of 62% of control values at 6 h. The decrease in pHVA was not affected by loading with DBQ (10 mg) 10 h previously (pHVA: 67.6 +/- 5.8% of preDBQ levels) or increasing the dose to 20 mg (56.1 +/- 11.8% of preDBQ levels) compared to a single 10 mg dose of debrisoquine (66.5 +/- 4.5% of preDBQ levels). pHVA was reduced in both de novo patients with Parkinson's disease and in healthy volunteers following DBQ (10 mg) administration. However, there was no difference in pHVA before or after DBQ administration when comparing the two groups. These results suggest that, following DBQ administration, pHVA does not reflect dopamine neuronal loss in de novo patients with Parkinson's disease, so it is unlikely to detect the disease before the clinical symptoms manifest themselves.

Adult↗

PubMed1993

Parallel alterations in Met-enkephalin and substance P levels in medial globus pallidus in Parkinson's disease patients.

Met-enkephalin (Met-enk) and substance P (SP) were measured by a combined high-performance liquid chromatography/radioimmunoanalysis method in medial (GPM) and lateral globus pallidus (GPL) from controls and from Parkinson's disease (PD) patients. All patients showed a similar marked (> 90%) reduction in dopamine (DA) levels in putamen compared with controls. However, based on DA levels in the caudate nucleus, two subgroups of PD patients were differentiated. In patients with > 80% decrease in caudate nucleus DA content, there was a three-fold increase in both Met-enk and SP levels in GPM. In contrast, in patients showing an approximately 50% reduction in DA content in caudate, levels of both peptides were markedly reduced (approximately 80%). Met-enk and SP levels in GPL were unchanged in PD. These results suggest that neurons containing Met-enk and SP projecting to GPM adapt according to the extent of degeneration in the substantia nigra in PD.

Aged↗

PubMed1993

Age-related effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment of common marmosets.

The effect of treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on juvenile (6-8 months), young adult (2-4 years) and aged (8-10 years) common marmosets were compared. Juvenile marmosets were more resistant to the actions of MPTP and required a greater cumulative dose over a longer period to induce the same degree of motor disability observed in older animals. Young adult and aged marmosets showed an equivalent motor recovery in the 4-5 weeks following cessation of MPTP treatment, but juvenile animals were less able to compensate for the motor impairments. Losses of putamen [3H]dopamine uptake and caudate nucleus dopamine content were equivalent in young adult and aged animals. However, juvenile animals showed a more marked degree of dopamine depletion and reduction in [3H]dopamine uptake. Histological analysis showed cell loss in the substantia nigra to be most prominent in juvenile animals although it was evident in all groups. No loss of cells in the locus coeruleus was apparent in any of the groups studied, and no intraneuronal eosinophilic inclusions were seen. Greater nigral cell loss and dopamine depletion were required in juvenile animals to impair motor function. The degree of behavioural recovery was less in juvenile animals than in young adult and aged marmosets. The extent of behavioural recovery appeared linked to the severity of cell loss and was not reduced in old age.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1993

Suppressive effect of L-dopa on dopamine cells remaining in the ventral tegmental area of rats previously exposed to the neurotoxin 6-hydroxydopamine.

Ever since the introduction of levo-3,4-dihydroxyphenylalanine (L-dopa) for the treatment of Parkinson's disease, there has been concern that it might accelerate the degeneration of dopamine neurones. Using rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle (MFB), we have studied the effect of chronic L-dopa treatment on the survival of dopamine cells which remain in the ventral tegmental area (VTA) ipsilateral to a 6-OHDA lesion. Following lesion surgery, rats were treated with L-dopa and carbidopa administered in the drinking water for 27 weeks. At the end of the treatment period, the number of dopamine cells remaining in each of the lesioned and intact substantia nigra (SN) and VTA were assessed, using tyrosine hydroxylase immunohistochemistry. Chronic L-dopa treatment resulted in an apparent reduction in the number of dopamine neurones remaining in the VTA ipsilateral to the lesion, whereas it had no effect on the number of dopamine cells remaining in the intact SN and VTA. This finding suggests a possible suppressive effect in vivo of L-dopa on dopamine cells in the midbrain of adult animals that have been previously exposed to 6-OHDA.

Animals↗

PubMed1993

Alterations in striatal and extrastriatal D-1 and D-2 dopamine receptors in the MPTP-treated common marmoset: an autoradiographic study.

In adult common marmosets (Callithrix jacchus), MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) treatment induced almost total depletion of cells in the substantia nigra pars compacts (SNc) but partial cell loss in the ventral tegmental area (VTA). There was severe depletion of [3H]-mazindol binding to dopamine (DA) uptake sites in the caudate, putamen, and SNc. The loss of [3H]-mazindol binding in the nucleus accumbens (NAc) and olfactory tubercle (OT) was less marked. [3H]-mazindol binding in the body of caudate nucleus showed a small but significant recovery with increasing post-lesion survival times. The specific binding of [3H]-SCH 23390 to D-1 DA receptor sites was increased after MPTP treatment in all subregions of both caudate and putamen but was unaltered in the NAc and OT. Substantia nigra pars reticulata (SNr), frontal cortex, and medial segment of globus pallidus (GPm) all demonstrated moderate levels of [3H]-SCH 23390 binding in control animals, which were unaffected by MPTP treatment. Specific [3H]-spiperone binding to D-2 DA receptor sites was not altered by MPTP treatment in the subregions of caudate-putamen. Moderate levels of [3H]-spiperone binding were observed in control animals in the NAc, OT, SNc, and the lateral segment of globus pallidus (GP1). [3H]-spiperone binding in the SNc and OT was partially decreased in MPTP-treated animals. The changes in specific [3H]-spiperone and [3H]-SCH 23390 binding induced by MPTP-treatment did not alter with post-lesion survival times. These results demonstrate that MPTP treatment causes greater dopaminergic denervation of the caudate-putamen than in NAc/OT. This resulted in an increase in postsynaptic D-1 DA receptor sites in the caudate-putamen but not in the NAc/OT. Also, there appeared to be loss of presynaptic D-2 DA receptor sites in the SNc and OT. In the caudate-putamen, the loss of presynaptic D-2 DA receptor sites may have masked postsynaptic D-2 DA receptor upregulation.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1993

Electromyographical differentiation of the components of perioral movements induced by SKF 38393 and physostigmine in the rat.

Facial electromyography (EMG) coupled with visual observation was used to investigate spontaneous and drug induced perioral movements in freely moving rats. Four separate perioral behaviours were identified; facial tremor, purposeless chewing, gaping and yawning. Facial tremor, yawning and gaping but not purposeless chewing produced characteristic EMG signals. Normal rats displayed a low level of purposeless chewing, occasional bursts of facial tremor but not gaping or yawning. Each burst of facial tremor was accompanied by a transient increase in purposeless chewing. Administration of the D1 agonist SKF 38393 induced a dose related increase in bursts of facial tremors and consequently an increase in the total number of purposeless chews. Gaping and yawning were not induced by SKF 38393 administration. Administration of the cholinesterase inhibitor physostigmine (0.1-0.4 mg/kg) induced a dose related increase in the total number of purposeless chews, but primarily these were not associated with facial tremor. Administration of physostigmine also increased gaping and yawning. Administration of the D1 antagonist SCH 23390 almost abolished facial tremor in normal treated rats but only partially reduced that induced by SKF 38393 and physostigmine. SCH 23390 reduced purposeless chewing in SKF 38393 treated rats but not in normal or physostigmine treated animals. Administration of the cholinergic antagonist atropine almost abolished facial tremor in normal and physostigmine treated rats, but only reduced by 46% that induced by SKF 38393. Atropine reduced purposeless chewing in normal, physostigmine and SKF 38393 treated animals. Physostigmine induced gaping and yawning were abolished by atropine administration.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1993

Effect of chronic trifluoperazine administration and subsequent withdrawal on the production and persistence of perioral behaviours in two rat strains.

The effect of chronic administration of trifluoperazine on the perioral movement profile of Wistar and Sprague-Dawley rats was examined. Perioral movements were characterised by visual observations, coupled with electromyographic recording from the masseter muscle. In drug-naive animals from both strains the spectrum of perioral behaviours was essentially identical, primarily consisting of purposeless chewing, accompanied by occasional bursts of facial tremor and teeth chattering, with occasional yawning. Each burst of facial tremor was accompanied by a transient increase in the rate of purposeless chewing. Wistar rats exhibited a higher level of spontaneous purposeless chewing compared to Sprague-Dawley rats. In both strains, chronic administration of trifluoperazine (5 mg/kg per day, PO) for 5 months induced an increase in perioral behaviour, which primarily consisted of enhanced purposeless chewing. In Wistar rats the drug-induced increase in purposeless chewing was accompanied by an increase in the incidence of yawning, with no change in the incidence of either facial tremor or teeth chattering. In contrast, Sprague-Dawley rats displayed a drug-induced increase in purposeless chewing, accompanied by an increase in the incidence of facial tremor and teeth chattering, but not yawning. In Wistar rats withdrawal of trifluoperazine diminished but did not reverse the drug-induced increase in purposeless chewing. Drug withdrawal also precipitated a transient increase in the incidence of facial tremor and teeth chattering, but had no effect on yawning. In Wistar rats, the level of purposeless chewing and the incidence of yawning remained elevated above control levels for at least 13 weeks after drug withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Reduction in cortical 5-HT3 binding sites following a unilateral 6-hydroxydopamine lesion of the medial forebrain bundle in rats.

Serotonergic mechanisms have been implicated in pathophysiology of Parkinson's disease, an illness where the dopamine deficiency represents the prime biochemical deficit. Present interest centres on the possible involvement of serotonergic receptors in modulating dopamine transmission. In this paper the binding of the selective 5-HT3 antagonist [3H]GR 65630 was studied in rats with a unilateral 6-hydroxydopamine lesion of the medial forebrain bundle. The maximal density of specific [3H]GR 65630 binding was reduced in homogenates of entorhinal (17.1%, P < 0.05) and prefrontal cortex (27.5%, P < 0.05) on the lesioned side of the rat brain compared to the control tissues. An increase in affinity for [3H]GR 65630 binding was also found in homogenates of prefrontal cortex (33.8%, P < 0.05). No changes in the characteristics of [3H]GR 65630 binding to homogenates from the amygdala and hippocampus were observed. These data suggest that altered dopamine function may affect serotonergic mechanisms in the cortex in Parkinson's disease.

Animals↗

PubMed1993

Altered muscarinic and nicotinic receptor densities in cortical and subcortical brain regions in Parkinson's disease.

Muscarinic and nicotinic cholinergic receptors and choline acetyltransferase activity were studied in postmortem brain tissue from patients with histopathologically confirmed Parkinson's disease and matched control subjects. Using washed membrane homogenates from the frontal cortex, hippocampus, caudate nucleus, and putamen, saturation analysis of specific receptor binding was performed for the total number of muscarinic receptors with [3H]quinuclidinyl benzilate, for muscarinic M1 receptors with [3H]pirenzepine, for muscarinic M2 receptors with [3H]oxotremorine-M, and for nicotinic receptors with (-)-[3H]nicotine. In comparison with control tissues, choline acetyl-transferase activity was reduced in the frontal cortex and hippocampus and unchanged in the caudate nucleus and putamen of parkinsonian patients. In Parkinson's disease the maximal binding site density for [3H]quinuclidinyl benzilate was increased in the frontal cortex and unaltered in the hippocampus, caudate nucleus, and putamen. Specific [3H]pirenzepine binding was increased in the frontal cortex, unaltered in the hippocampus, and decreased in the caudate nucleus and putamen. In parkinsonian patients Bmax values for specific [3H]oxotremorine-M binding were reduced in the cortex and unchanged in the hippocampus and striatum compared with controls. Maximal (-)-[3H]nicotine binding was reduced in both the cortex and hippocampus and unaltered in both the caudate nucleus and putamen. Alterations of the equilibrium dissociation constant were not observed for any ligand in any of the brain areas examined. The present results suggest that both the innominatocortical and the septohippocampal cholinergic systems degenerate in Parkinson's disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗

PubMed1993

Chronic administration does not alter the pharmacokinetic profile of L-dopa in the rat.

Chronic administration of L-dopa (200 mg kg-1 day-1 for 12 months) plus carbidopa (25 mg kg-1 day-1) or carbidopa (25 mg kg-1 day-1) alone did not alter the t1/2, AUC0-infinity k10, k12, k21, CLp or Vdss of L-dopa following intra-aortic (i.a.) administration (50 mg kg-1) alone or after carbidopa (25 mg kg-1, i.p.) pretreatment, or the t1/2, AUC0-infinity, tmax or the bioavailability (F) of L-dopa (50 mg kg-1) administered orally, alone or after acute pretreatment with carbidopa (25 mg kg-1 i.p.). The peripheral metabolism of L-dopa was unaltered by chronic administration of L-dopa plus carbidopa or carbidopa alone as measured by unaltered AUC0-360 min for 3-O-methyldopa, dopamine, DOPAC or homovanillic acid in the plasma of rats following acute administration of L-dopa (50 mg kg-1, p.o. or i.a.) alone or following pretreatment with carbidopa, and unaltered hepatic dopa decarboxylase activity.

Administration, Oral↗