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Biomedical subjects

C D Marsden

Publications and source records attributed to C D Marsden.

At least 595 records · Page 33Linked to original sources
PubMed1987

Wilson's disease.

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Hepatolenticular Degeneration↗
PubMed1987

Multivariate statistical analysis of L-dopa esters as potential anti-parkinsonian prodrugs.

This paper reports a QSAR study of thirteen L-DOPA esters previously synthesised and examined for their physicochemical, biochemical and behavioural properties. Multivariate statistical analysis (principal component analysis, cluster analysis, simple and multiple linear regression) reveals favourable and unfavourable structural features of L-DOPA prodrugs. Some of the many biochemical and behavioural activities investigated are shown to be redundant. These indications may contribute to the design of novel L-DOPA prodrugs.

Analysis of Variance↗
PubMed1986

Alterations in [Met5]- and [Leu5]enkephalin and neurotensin content in basal ganglia induced by the long-term administration of dopamine agonist and antagonist drugs to rats.

Treatment of rats for 18 months with trifluoperazine increased [Met5]- and [Leu5]enkephalin and neurotensin content in striatum and nucleus accumbens. However, in substantia nigra the content of [Met5]enkephalin was decreased, [Leu5]enkephalin unchanged and that of neurotensin increased. Administration of L-DOPA plus carbidopa, bromocriptine or pergolide for 12 months decreased [Met5]enkephalin (except bromocriptine) and neurotensin, but not [Leu5]enkephalin, levels in striatum. L-DOPA decreased and bromocriptine increased neurotensin levels in substantia nigra. But neurotensin levels in nucleus accumbens were unaffected.

Animals↗
PubMed1986

Hypophysectomy may non-selectively alter pharmacokinetic parameters to enhance the ability of haloperidol to increase striatal dopamine receptor density in the rat.

We have investigated the effect of a range of doses of haloperidol (0.625-5.0 mg/kg/day) or saline, administered for 14 days, followed by a 3 day drug washout period, to sham operated or hypophysectomized rats. Haloperidol increased the number of specific striatal 3H-spiperone binding sites (Bmax) in sham-operated animals at doses of 2.5 and 5.0 mg/kg/day, and in hypophysectomized animals at all doses used (0.625-5.0 mg/kg/day). The inhibition of locomotor activity produced by haloperidol was greater in hypophysectomized than sham-operated animals. Plasma and striatal haloperidol levels after equivalent doses were greater in hypophysectomized than in sham-operated animals. We conclude that hypophysectomy may enhance the ability of haloperidol to induce striatal dopamine receptor supersensitivity in the rat, and that this may be due to differences in the pharmacokinetic handling of haloperidol between sham-operated and hypophysectomized animals.

Animals↗
PubMed1986

Hyperprolactinaemia does not alter specific striatal 3H-spiperone binding in the rat.

We have investigated the effect of single injections (1 mg/animal i.v.) of prolactin or vehicle, and repeated depot (0.125-1.0 mg/animal/day) or bolus (1.0 mg/animal/day) administration of prolactin or vehicle for 6 days to adult male rats. The density (Bmax) and affinity (Kd) of specific striatal [3H]spiperone binding was not changed by any of the prolactin treatment schedules used. Allogeneic transplants of anterior pituitary glands resulted in an increased concentration of circulating prolactin but did not alter the density or affinity of specific striatal [3H]spiperone binding in male rats, measured 2 weeks following the operation. Prolactin did not displace specific striatal [3H]spiperone binding when incorporated in vitro. Any effect of prolactin on striatal dopamine receptor function appears to be exerted only by high, non-physiological concentrations, and such effects are difficult to reproduce.

Animals↗
PubMed1986

Acute and repeated administration of sulpiride alters Met-and Leu-enkephalin content of rat brain.

Following acute administration of sulpiride (100 mg/kg, i.p.), Met-enkephalin levels were increased in striatum but decreased in substantia nigra and nucleus accumbens. No effect was observed in hypothalamus or frontal cortex. In contrast, Leu-enkephalin content was decreased in the nucleus accumbens but not elsewhere. Administration of sulpiride (10 or 100 mg/kg, i.p.) for 21 days, followed by 2 days drug withdrawal, caused a dose-dependent increase in Met-enkephalin in nucleus accumbens but decreases in hypothalamus and frontal cortex. No change was observed in the striatum or substantia nigra. Repeated sulpiride administration caused a decrease in Leu-enkephalin content of the hypothalamus and cortex but not elsewhere.

Animals↗
PubMed1986

The neurotoxic actions of 6-hydroxydopamine infused into the rat substantia nigra.

6-Hydroxydopamine (6-OHDA) 10 and 40 micrograms/24 h infused bilaterally for 4 days into the rat substantia nigra (SN) caused a 'freezing' akinetic response which was apparent within 24 h and which persisted throughout the period of infusion. The infusion of 10 or 40 micrograms/24 h 6-OHDA into the SN failed to cause any change in motor coordination, or induce limb and body rigidity. The infusion of 40 micrograms/24 h 6-OHDA led to significant reductions in the striatal levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid and noradrenaline; no changes were observed following the 4-day infusion of 10 micrograms 6-OHDA. The consequences of infusing 6-OHDA into the SN are discussed in relation to those induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridine (MPP+) where the spectrum of behavioural and biochemical change caused by 6-OHDA is shown not to mimic the actions of either MPTP or MPP+.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Painful Parkinson's disease.

A number of patients with Parkinson's disease complain of severe and distressing pain. Many of them are referred for psychiatric or other inappropriate treatment. The key diagnostic clue to the origin of the pain is that in almost all cases it fluctuates in parallel with the motor changes associated with levodopa treatment. The nature of this temporal association in the individual case, as well as aiding diagnosis, often indicates the need for appropriate modifications in antiparkinsonian therapy, which can be far more effective than conventional analgesic treatments.

Acute Disease↗
PubMed1986

The dopamine neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces histological lesions in the hypothalamus of the common marmoset.

The administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to marmosets resulted in parkinsonism and degeneration of the substantia nigra pars compacta. Examination of the hypothalamus showed neuronophagic-like rosettes of glial cells and diffuse increase in glial numbers in areas of the dopaminergic A11-A14 groups. These findings suggest that MPTP may be toxic to dopamine neurons of the hypothalamus as well as to the substantia nigra.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Alterations in motor behaviour produced by the isomers of 3-PPP in the MPTP-treated marmoset.

Alterations in motor activity induced by the isomers of 3-(3-hydroxyphenyl)-N,n-propylpiperidine (3-PPP) were studied in normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated marmosets. In both normal and MPTP-treated animals motor activity was suppressed in a dose-dependent manner by the administration of (-)-3-PPP. In control animals (+)-3-PPP caused biphasic changes in motor activity, namely suppression of activity in low doses but stimulation at higher doses. In contrast (-)-3-PPP only caused locomotor stimulation in MPTP-treated marmosets. (+)-3-PPP may potentially be of use as a post-synaptic dopamine agonist drug in Parkinson's disease.

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