Muscarinic antagonists antiparkinsonian

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 interneurons 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. 

Another compound structurally related to this series is the aminoethyl analogue of (R)-HHD, i.e. the (R)-enantiomer of the antiparkinsonian drug trihexyphenidyl (7, THP). (R)-TID proved to be an Mj-selective muscarinic antagonist with intermediate afiMty at M3 and at M4 and low affinity at M2 receptors. However, its stereoselectivity profile (R/S) of Mj=M3=M4> M2 is ver similar to that of HHD (Figure 4) [39]. 

Antagonists of muscarinic acetylcholine receptors had widely been used since 1860 for the treatment of Parkinson s disease, prior to the discovery of l-DOPA. They block receptors that mediate the response to striatal cholinergic interneurons. The antiparkinsonian effects of drugs like benzatropine, trihexyphenidyl and biper-iden are moderate the resting tremor may sometimes respond in a favorable manner. The adverse effects, e.g., constipation, urinary retention, and mental confusion, may be troublesome, especially in the elderly. 

Benadryl diphenhydramine, benaprizine benapryzine. benapryzine [ban] (benaprizine [inn] benapryzine hydrochloride [usan]) is a benzilate, a muscarinic CHOLINOCEPTOR ANTAGONIST which has been used as an ANTIPARKINSONIAN AGENT. 

Dexedrine dexamphetamine, dexetimide [ban, inn, usan] (benzetimide [inn] benzetimide hydrochloride [usan]) is a tertiary amine substituted piperidine, a MUSCARINIC cholinoceptor ANTAGONIST and ANTIPARKINSONIAN AGENT. It iS the (i)-form, the pharmacologically more active enantiomer. The (R)-form is levetimide. 

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