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Biomedical subjects

A V Mackay

Publications and source records attributed to A V Mackay.

At least 19 recordsLinked to original sources
PubMed1992

Dopamine receptor abnormalities in the striatum and pallidum in tardive dyskinesia: a post mortem study.

Dopamine D1 and D2 receptors were determined in brain tissue taken post mortem from schizophrenic patients previously known to have had tardive dyskinesia and yet who had not received neuroleptic drug treatment for over one year prior to death. In comparison with age-matched control subjects, diminished D2 receptor density was observed in striatal regions, while these receptors appeared to be increased in the pallidum, an area of the brain particularly implicated in the production of dyskinesias. D 1 receptors showed similar tendencies to lower numbers in the striatum in tardive dyskinesia.

Aged↗
PubMed1985

New antipsychotic agents and the future.

In the absence of knowledge about the etiology of the diseases being treated and of adequate animal models, the future design of antipsychotic agents must rely largely on a pragmatic extension from the drugs already known to be useful. The property of dopamine receptor antagonism has proved a reliable predictor of antipsychotic effect. It may be argued that further therapeutic gains through development of more selective and more potent dopamine antagonists are unlikely. A general limitation of receptor-active drugs is the phenomenon of reactive change in receptor numbers. For long-term maintenance treatment, it may be sensible to search for a neuroleptic equivalent of lithium, which has no direct effect on membrane receptors. The two most pressing clinical issues are 1) persuading clinicians to use the minimum effective clinical dose for the shortest time, and 2) developing an effective treatment for the schizophrenic defect state, its possible association with cerebral atrophy notwithstanding.

Amygdala↗
PubMed1982

Increased brain dopamine and dopamine receptors in schizophrenia.

In postmortem samples of caudate nucleus and nucleus accumbens from 48 schizophrenic patients, there were significant increases in both the maximum number of binding sites (Bmax) and the apparent dissociation constant (KD) for tritiated spiperone. The increase in apparent KD probably reflects the presence of residual neuroleptic drugs, but changes in Bmax for tritiated spiperone reflect genuine changes in receptor numbers. The increases in receptors were seen only in patients in whom neuroleptic medication had been maintained until the time of death, indicating that they may be entirely iatrogenic. Dopamine measurements for a larger series of schizophrenic and control cases (n greater than 60) show significantly increased concentrations in both the nucleus accumbens and caudate nucleus. The changes in dopamine were not obviously related to neuroleptic medication and, unlike the receptor changes, were most severe in younger patients.

Adolescent↗
PubMed1979

Tardive dyskinesia.

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Antipsychotic Agents↗
PubMed1979

Alterations in [3H]spiperone binding in human caudate nucleus, substantia nigra and frontal cortex in the Shy-Drager syndrome and Parkinson's disease.

[3H]Spiperone binding was investigated in the caudate nucleus, substantia nigra (s. nigra) and frontal cortex of control subjects and of patients with Parkinson's disease and the Shy-Drager syndrome. Binding sites for [3H]spiperone were interpreted as dopamine receptors in caudate and s. nigra, and as 5-hydroxytryptamine (5-HT) receptors in frontal cortex. Scatchard analysis showed that the Bmax (maximal number of binding sites) in caudate was similar in the 3 groups, whereas in s. nigra the Bmax was reduced by approximately 60% in both Parkinsons disease and Shy-Drager syndrome. The dissociation constant (Kd) for [3H]spiperone binding in s. nigra was similar in the 3 groups. In caudate nucleus, the Kd was similar in control and Parkinson groups; however, there was a significant increase in the dissociation constant in the caudate nucleus from cases of Shy-Drager syndrome. No differences in binding characteristics were observed in the frontal cortex. These results are taken to reflect a loss of dopamine receptor sites in the s. nigra in both Parkinson's disease and Shy-Drager syndrome, and a reduced affinity of dopamine receptor sites in the caudate nucleus in Shy-Drager syndrome.

Binding Sites↗
PubMed1979

Pharmacotherapeutic trials in tardive dyskinesia.

Some of the clinical factors contributing to the currently unsatisfactory state of therapy for tardive dyskinesia are reviewed. Problems such as lack of clear syndrome delineation and phenomenological description, the lack of standardization in rating scales and the lack of attention to trial design have all probably contributed to a rather confusing picture. Controlled trials suggest that several pharmacological agents may be of therapeutic value but that clinical prediction of an individual's response is impossible. The strategy of acute drug challenge has emerged as perhaps the most promising approach to the definition of pharmacological subtypes and therefore the choice of optimal treatment.

Acetylcholine↗