Metabolic effects of scopolamine and physostigmine in human brain measured by positron emission tomography

Blin, J.; Piercey, Montford F.; Giuffra, M.; Mouradian, M. Maral; Chase, Thomas N.

doi:10.1016/0022-510x(94)90202-x

Cited by 24 publications

(13 citation statements)

References 38 publications

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“…Blin et al (1994) That group did report weak reductions in prefrontal cortex, consistent with the location of our findings.…”

Section: Comparison With Previous Reportssupporting

confidence: 80%

“…It is, therefore, difficult to explain the paradoxical increase of cortical metabolism by scopolamine reported by Blin et al (1994). Their dose of 0.25 mg/m 2 of body surface area would result in about 0.43 mg in a stan dard adult, �20% lower than our dose of 7.2 jLg/kg; furthermore, they administered it by slow infusion, whereas ours was a bolus injection.…”

Section: Comparison With Previous Reportsmentioning

confidence: 51%

“…Because it is the only such experiment in the literature, it is reviewed in some detail. Using 2-deoxy-2-fluoro-o-glucose positron emission tomography (FDG-PET) proce dures, Blin et al (1994) reported that scopolamine increased glucose metabolism throughout the cortex in elderly healthy subjects, whereas physostigmine administration to AD patients resulted in slight de creases in the posterior cortex and increases in the frontal cortex. Our physostigmine effects are consis tent with these findings in their regional distribution, although the changes observed by Blin et al (1994) were much weaker and did not reach significance.…”

Section: Comparison With Previous Reportsmentioning

confidence: 99%

“…Dauphin et al (1991) In fact, these authors showed that the elimination half-life of physostigmine from most cortical areas (other than occipital and olfactory) ranged from 4 to 10 min. The FDG procedure is usually insensitive to rapid changes, and Blin et al (1994) were forced to reduce the dose and prolong the scan further to allow for two measurements. Therefore, a transient effect could have been missed.…”

Section: Comparison With Previous Reportsmentioning

confidence: 99%

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Physostigmine Reversal of Scopolamine-Induced Hypofrontality

Prohovnik¹,

Arnold²,

Smith³

et al. 1997

J Cereb Blood Flow Metab

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The muscarinic receptor antagonist scopolamine produces a transient memory deficit in healthy humans. This deficit has been offered as a model of the cholinergic deficit of Alzheimer's disease (AD). However, we have previously shown that scopolamine produces a deficit of cortical perfusion maximal in the frontal lobe, dissimilar to the parietal cortex deficit characteristic of AD. The current experiment was aimed at replicating and extending this observation by critically testing the central cholinergic origin of both cognitive and perfusion deficits. Nine healthy subjects participated in regional cerebral blood flow (rCBF) measurements at baseline, after scopolamine (7.2 μg/kg i.v.), and after both physostigmine (22 μg/kg i.v.) and neostigmine (7 or 11 μg/kg i.v.). rCBF was quantified by the xenon 133 inhalation method. As expected, scopolamine reduced cortical perfusion, mainly in the frontal cortex, and produced a memory deficit. Physostigmine, but not neostigmine, reversed all three variables partially or completely. These results support the hypothesis that all three consequences of scopolamine, namely, reduction of mean flow, frontal deficit, and memory impairment, are cholinergically mediated. Furthermore, because neostigmine poorly crosses the blood–brain barrier, these findings confirm that the effect is centrally mediated and cannot be explained by peripheral effects. However, they also confirm the frontal cortex locus of action for both scopolamine and its reversal by physostigmine and therefore suggest a major dissimilarity to the characteristic rCBF appearance of AD. This study extends our previous preliminary findings with tacrine and strengthens the suggestion that only nicotinic receptors are associated with the characteristic parietal deficit of AD.

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“…Blin et al (1994) That group did report weak reductions in prefrontal cortex, consistent with the location of our findings.…”

Section: Comparison With Previous Reportssupporting

confidence: 80%

Section: Comparison With Previous Reportsmentioning

confidence: 51%

Section: Comparison With Previous Reportsmentioning

confidence: 99%

Section: Comparison With Previous Reportsmentioning

confidence: 99%

See 2 more Smart Citations

Physostigmine Reversal of Scopolamine-Induced Hypofrontality

Prohovnik¹,

Arnold²,

Smith³

et al. 1997

J Cereb Blood Flow Metab

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“…Each group of subjects showed a signiÞcant decrease of their brain glucose consumption under treatment (Tables 4 and 5). These Þndings conÞrm in AD and extend to normals the previous depressive e¤ect of physostigmine found previously in the cerebral cortex of a group of Alzheimer patients (Blin et al 1994). Compared to this previous work, the depressive e¤ect of physostigmine was found to be larger in the present group of Alzheimer patients.…”

Section: Discussionmentioning

confidence: 89%

Physostigmine results in an increased decrement in brain glucose consumption in Alzheimer's disease

Blin¹,

Ivanoiu²,

Volder³

et al. 1998

Psychopharmacology

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The responsibility of cerebral cholinergic lesions for the weak clinical response to cholinergic neurotransmission enhancement of Alzheimer's disease (AD) was studied by measuring the effects of physostigmine on glucose consumption and neuropsychological tests. Ten AD and ten aged normals (AN) were examined twice, under placebo and under maximal tolerated dose of physostigmine, in randomized order and blind fashion. Under physostigmine, both groups showed better performances in tests measuring attention (P < 0.05-0.001) but not long-term memory, and cerebral glucose consumption was regionally modified (P < 0.0001). We observed a regional decrease in AD and in AN which was larger in AD, where each patient exhibited a mean metabolic decrease. With normalized values, AD and AN showed a similar decrease in the metabolic values of prefrontal cortex and striatum (P = 0.0003). These findings suggest that cholinergic neurotransmission enhancement depresses glucose consumption and increases selective attention in similar ways in both groups, but to a larger extent in AD. This suggests that brain metabolism in AD over-responds to enhancement of cholinergic neurotransmission. The observed weak response of clinical symptomatology to anticholinesterase agents does not appear to be due to the failure to enhance the activity of the cholinergic system in AD.

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