Alzheimer’s Disease

on 9.3.06 with 0 comments



We don’t know the exact trigger of this disease, but we’ve found that there is a relative deficiency of brain Acetylcholine in Alzheimer’s patients’ autopsied brains. We can get acetylcholine to accumulate in the brain by giving some anticholinesterase agents that are relatively selective for the CNS cholinesterase. The two drugs are Tacrin (Cognex) and Donepezil (Aricept), and are widely seen in therapeutics. They are anticholinesterase agents intended to increase cholinergic transmission in the brain and hopefully increase memory. These drugs really aren’t that specific for brain cholinesterase though, and again there are systemic side effects.



Now we’ll talk about hypotension. One issue that led to a nobel prize was the discovery that on vascular smooth muscle there were muscarinic receptors. When acetylcholine was applied to these muscarinic receptors there was vasodilation! A substance derived from the endothelium was produced (not from the smooth muscle, but from the endothelium) which released a factor—Endothelium Dependent Releasing Factor (EDRF). EDRF turns out to be Nitric Oxide (NO). So the endothelium produces NO, which comes back to act on the smooth muscle for vasodilation. So cholinergic vasodilation, muscarinic mediated, caused by the production of nitric oxide. Turns out that dozens of other systems also utilize nitric oxide.

Category: Pharmacology Notes

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