Antagonists of the muscarinic cholinergic receptor

QAs exert a blocking effect oti the nicotinic cholinergic receptor and they are weak antagonists at the muscarinic cholinergic receptor [42], displaying similar agonistic activities as the alkaloid nicotine. Neurological (weakness, dizziness, mydriasis, anxiety, confusion, malaise, loss of coordination, visual disturbances. 

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. 

Worsening parkinsonism was observed in two patients after treatment with olanzapine 5 mg/day (114). In contrast, coarse tremors induced by fluphenazine or haloper-idol disappeared in three patients within days of the start of treatment with olanzapine (10 mg/day), without discontinuation or reduction in the dosage of fluphenazine or haloperidol (115). Olanzapine is active at muscarinic cholinergic receptors, which may account for the observed suppression of neuroleptic drug-induced tremor however, two of the three patients had been taking ben-zatropine, an antagonist at muscarinic acetylcholine receptors, with little tremor relief, suggesting that olanzapine could suppress tremor by means of an action other than muscarinic blockade. 

Cholinergic receptors in iris sphincter tissue and ciliary body have been shown to be of the muscarinic type. Five muscarinic receptor subtypes (M1-M5) have been identified. Sixty percent to 75% of the muscarinic receptors in the human iris sphincter and ciliary body are M3, and 5% to 10% are M2 and M4. Approximately 7% of receptors in the ciliary processes and iris sphincter are of the Ml subtype. Approximately 5% of receptors present in the iris sphincter are M5. Inhibition of these receptors by cholinergic antagonists induces pupillary dilation (mydriasis) and paralysis of accommodation (cycloplegia) and may elevate intraocular pressure (lOP), particularly in patients with predisposing risk factors. 

ACh acts at two different types of cholinergic receptors Muscarinic and Nicotinic receptors. Muscarinic receptors (1) bind ACh as well as other agonists (muscarine, pilocarpine, bethan-echol) and antagonists (atropine, scopolamine). There are at least 5 different types of muscarinic receptors (M1-M5) and all have slow response times. They are coupled to G-proteins and a variety of second messenger systems. When activated, the final effect can be an opening or closing of channels for K", Ca ", or Cl . Presynaptic cholinergic receptors are of the muscarinic or nicotinic type and can modulate the release of several neurotransmitters. 

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