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Biomedical subjects

C D Marsden

Publications and source records attributed to C D Marsden.

At least 901 records · Page 50Linked to original sources
PubMed1978

The effect of chronic administration and withdrawal of amphetamine on cerebral dopamine receptor sensitivity.

Mice with a 6-hydroxydopamine induced unilateral nigro-striatal lesion received (+)-amphetamine sulphate (2.5-20 mg/kg) over a 3-month period by daily incorporation into the drinking water. Druing this period the circling response to apomorphine hydrochloride (0.01-0.5 mg/kg, s.c.) was increasingly suppressed in comparison to control animals, while spontaneous locomotor activity increased. Following drug withdrawal the circling response to apomorphine remained suppressed two months later. However, spontaneous locomotor activity was also reduced up to 1 month following drug removal. The dopamine content of the lesioned side of the forebrain was 25% of the intact side in control animals and was not further reduced by amphetamine administration. The dopamine content of the intact forebrain was reduced by 43% during amphetamine administration and remained 18% depressed 1 month following drug withdrawal. No changes in 5-hydroxytryptamine or noradrenaline concentrations were observed in either the intact or lesioned side. This data, while showing that chronic amphetamine treatment can induce persistent changes in dopamine receptor sensitivity, can be interpreted in terms of increased striatal receptor sensitivity or as a decreased response of dopamine receptors in the nucleus accumbens.

Animals↗
PubMed1978

Effect of new dopamine-blocking agent (oxiperomide) on drug-induced dyskinesias in Parkinson's disease and spontaneous dyskinesias.

Oxiperomide, a new dopamine-receptor antagonist, was found to decrease dyskinesias in patients with Parkinson's disease receiving levodopa or other dopamine agonists without necessarily increasing Parkinsonian symptoms. Oxiperomide also decreased spontaneous dyskinesias in those with tics and chorea and to a less extent in those with torsion dystonia, without necessarily causing Parkinsonism. These results provide evidence that more than one population of dopamine receptors exist in the extra pyramidal system, and encourage the search for selective dopamine antagonists.

Aged↗
PubMed1978

The rotating rodent: a two component system?

The hypothesis that the rotating rat requires both nigro-striatal and mesolimbic dopaminergic components for activity has been tested. 6-Hydroxydopamine lesions were induced unilaterally in either or both the ascending nigrostriatal and mesolimbic dopamine pathway. In one group of rats the nucleus accumbens was destroyed bilaterally with electrolesions. Circling behaviour was only recorded when there was both an imbalance in striatal dopamine concentrations concomitant with stimulation of the limbic dopamine regions. Lesions of the mesolimbic dopamine pathway resulted in changes in drug-induced motor activity but postural asymmetry or circling behaviour was not observed. The results support the hypothesis that the rotating rodent requires two functional dopamine components: striatal dopamine imbalance causing a postural asymmetry and stimulation of mesolimbic dopamine systems providing a locomotor component. The relevance of these components in this animal model is discussed with reference to dopaminergic agonist and antagonist drugs.

Animals↗
PubMed1978

5-hydroxytryptophan-induced myoclonus in guinea pigs. A physiological and pharmacological investigations.

5-Hydroxytryptophan (5-HTP) induces a characteristic behavioural syndrome of altered motor activity with muscle jerking in guinea pigs. Myoclonic jerking occurs synchronously in forelimbs and hindlimbs and is associated with a stereotyped electromyographic (EMG) pattern of a burst of activity lasting 40-50 msec in active muscles, followed by silence lasting 50-70 msec, followed by a further variable period of muscle activity. Such myoclonus may be induced also by the administration of L-tryptophan plus a monamine oxidase inhibitor (MAOI), or by agents acting as serotonin (5-HT) receptor agonists. The 5-HTP-induced syndrome is antagonised by a central decarboxylase inhibitor (NSD-1035) and by agents which block 5-HT receptors (methysergide and cyproheptadine). 5-HTP-induced jerking is abolished below the level of a spinal cord transection, but persists in decerebrate animals. No electroencephalographic (EEG) changes are seen preceding the muscle jerks. The clinical significance of this animal model of myoclonus is discussed.

5-Hydroxytryptophan↗
PubMed1978

Plasma bromocriptine levels, clinical and growth hormone responses in Parkinsonism.

1. Plasma bromocriptine levels following separate oral doses of bromocriptine 12.5, 25, 50 and 100 mg have been determined in ten subjects with parkinsonism. 2. There was considerable variation between peak plasma bromocriptine levels in individual subjects after similar doses of bromocriptine. Peak levels occurred 30--210 min after dosage (mean 102 min). Peak clinical response, peak rise in plasma growth hormone level and fall in blood pressure followed shortly after peak bromocriptine levels occurred. 3. The shape of the plasma-time curve for bromocriptine was similar with all dosages. 4. There was no significant relationship between peak plasma bromocriptine levels, peak clinical response, peak increase in growth hormone and peak fall in blood pressure. However, the degree of improvement in the signs of parkinsonism was related to plasma bromocriptine levels was achieved. 5. Metoclopramide 60 mg pretreatment had no consistent effect upon plasma bromocriptine levels, the clinical or hormonal response.

Aged↗
PubMed1978

Functional changes in cerebral 5-hydroxytryptamine metabolism in the mouse induced by anticonvulsant drugs.

1 Acute administration of clonazepam, diazepam, and diphenylhydantoin to mice elevated cerebral 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA); chronic administration had less effect. 2 Acute administration of clonazepam and diazepam but not diphenylhydantoin raised cerebral trytophan levels; chronic administration of clonazepam caused a smaller elevation of cerebral tryptophan but chronic administration of diazepam still caused a large rise in cerebral tryptophan. 3 Neither clonazepam nor diazepam caused induction of drug metabolizing enzymes on chronic administration but diphenylhydantoin had a marked effect. 4 These data suggest that the altered 5-HT metabolism caused by these compounds is unrelated to a common action on tryptophan levels, and that the reduced effect of clonazepam and diazepam on chronic administration cannot be attributed to increased metabolism of these compounds. 5 Clonazepam induced abnormal head movements in mice in a dose-dependent manner. Pretreatment of animals with tranylcypromine increased the intensity of movement, although pargyline was without effect. Similar effects were observed with diazepam and diphenylhydantoin, suggesting that the increase in cerebral 5-HT caused by these compounds is of functional significance in stimulating 5-HT receptors.

Animals↗
PubMed1978

Sodium valproate in the treatment of levodopa-induced dyskinesia.

The effect of sodium valproate 1200 mg daily on the disability of Parkinsonism and on levodopa-induced dyskinesia was assessed in a double-blind crossover trial with matched placebo in 12 patients with Parkinson's disease. No objective change in the severity of Parkinsonism or dyskinesias was noted. However, six out of nine patients who completed the trial noted a slight to moderate improvement in their dyskinesias with no change in their Parkinsonism. Excess salivation improved in four subjects on sodium valproate.

Clinical Trials as Topic↗