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Muscarinic Versus Nicotinic Modulation of a Visual Task: A PET Study Using Drug Probes

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Little is known about acetylcholine (ACh) modulation of central visual processing in humans. Receptor densities in visual brain regions are differentially distributed suggesting that receptor subtypes have different functions. Using PET, we have previously described the brain regions activated by a simple pattern-flash stimulus in healthy elderly subjects. To evaluate muscarinic and nicotinic contributions to ACh modulation of visual processing, we scanned elderly subjects watching the pattern-flash stimulus during no drug, during physostigmine augmentation, and during scopolamine antagonism of physostigmine's action. These manipulations of ACh significantly altered regional cerebral blood flow (rCBF) in brain regions activated by the task. The pattern of rCBF values across drug conditions suggested that muscarinic and nicotinic effects were dissociated. Muscarinic action predominated in striate cortex (Brodmann Area, BA 17) and lateral visual association areas (BA 18, 19), while nicotinic action predominated in the thalamus and inferior parietal regions (BA 39/40). Both muscarinic and nicotinic actions increased rCBF in some regions while decreasing it in others. A parsimonious reconciliation of these results with functional anatomy suggests that muscarinic action modulates visual attribute processing, while nicotinic action modulates arousal and selective attention to the visual task.





I'd suggest reading the entire article.


Though Coluracetam didn't quite seem to cut it, I do see potential for selective Muscarinic agents, possibly particularly for the M1 subunit.

Xanomeline is one such agent that activates M1, although it's non-selective, moreover also antagonizes M5, and also has a high drop-out rate due to adverse events. Unfortunately, most other muscarinic agents are either not centrally active, or are antagonists. I still have to look in to Vedaclidine, which may or may not be centrally active; this is not clear from an initial glance. To be fair, however, other subtypes still warrant investigation.

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