Anticholinergic Drugs

Before the introduction of levodopa, the belladonna alkaloids (e.g., atropine and scopolamine) were the primary agents used in the treatment of parkinsonism. The belladonna alkaloids have been replaced by anticholinergic agents with more selective central nervous system (CNS) effects. Trihexyphenidyl (Artane), ben-ztropine mesylate (Cogentin), biperiden (Akineton), and procyclidine (Kemadrin) are useful in most types of parkinsonism.

The efficacy of anticholinergic drugs in parkinsonism is likely due to the ability to block muscarinic receptors in the striatum. In the absence of the inhibitory action of dopamine, the actions of the intrastriatal cholinergic in-terneurons are unopposed, yielding enhanced stimulation of muscarinic receptors. Blockade of these receptors reduces striatal activity. The muscarinic antagonists exert only modest antiparkinsonian actions and thus are most commonly used during the early stages of the disease or as an adjunct to levodopa therapy.

Of the drugs used for treating parkinsonism, the anticholinergics are the only class that can provide benefit in the treatment of the drug-induced parkinsonism seen with antipsychotic therapy. This is because the blockade of dopamine receptors by the antipsychotics leads to increased activity of the striatal neurons. Blockade of the muscarinic receptors reduces this excitatory activity.

The adverse effects of the anticholinergic drugs are due to their antimuscarinic effects in other systems (e.g., cycloplegia, dry mouth, urinary retention, and constipation). Confusion, delirium, and hallucinations may occur at higher doses.

The antihistamine diphenhydramine (Benadryl), because it has anticholinergic properties, is used for mild parkinsonism and with the elderly, who may not be able to tolerate the more potent anticholinergics, levodopa, or the dopamine agonists.

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