20.2.2.4 Treatment to Inhibit the Cholinergic System

When the dopaminergic system becomes underactive in Parkinson’s disease, it leaves the cholinergic system unopposed, and this produces an apparently overactivity cholinergic system. Thus, another approach to the treatment of Parkinson’s disease is to inhibit the cholinergic system.

Four, possibly 5, of the muscarinic subtypes are present in the striatum. However, inhibition of muscarinic receptors only has a modest benefit in Parkinson’s disease. Thus, the antimuscarinic agents are not used alone in Parkinson’s disease, but rather can be used as an adjunct to L-DOPA based therapy. Thus, when the L-DOPA/carbidopa effect is waring off, antimuscarinic agent may be added.

To be effective in the treatment of Parkinson’s disease, it is necessary to have an antimuscarinic agent that crosses the blood brain barrier. Benzotropine crosses the blood brain barrier and is used in the treatment of Parkinson’s disease. Some of the adverse effects observed with benzotropine are due to central anti-muscarinic activity e.g. sedation and mental confusion. Benzotropine will also be found in the periphery after oral administration. Consequently, adverse effects are observed to benzotropine which are due to peripheral anti-muscarinic activity e.g. constipation, urinary retention, and blurred vision through cycloplegia.