Muscarinic targets

The drug serves as a potential muscarinic agonist which is found to be totally devoid of the nicotinic activity but is found to be nonselective with regard to the muscarinic targets. Pilocarpine nitrate is observed to penetrate membranes in a much better and efficient manner than do quaternary ammonium cholinomimetics perhaps due to its basic tertiary amine characteristic feature. 

Alkaloids are heterocyclic basic compounds and widespread in plants. Many of them have specific targets in organisms. For example, the alkaloids atropine and scopolamine of Belladonna are specific antagonists at muscarinic receptors. 

Both nicotinic and muscarinic receptors are widespread in the CNS. Muscarinic receptors with a high affinity for pirenzepine (PZ), M, receptors, predominate in the hippocampus and cerebral cortex, whereas M2 receptors predominate in the cerebellum and brainstem, and M4 receptors are most abundant in the striatum. Central muscarinic and nicotinic receptors are targets of intense pharmacological interest for their potential roles in regulating abnormal neurological signaling in Alzheimer s disease, Parkinson s disease and certain seizure disorders. Nicotinic receptors are largely localized at prejunctional sites and control the release of neurotransmitters [10,11],... 

Lack of selectivity (C). Despite appropriate dosing and normal sensitivity, undesired effects can occur because the drug does not specifically act on the targeted (diseased) tissue or organ. For instance, the antichoUnergic, atropine, is bound only to acetylcholine receptors of the muscarinic type however, these are present in many different organs. 

Target tissues of 2"" parasympathetic neurons ACh Muscarine Atropine Muscarinic (M) cholinoceptor G-protein-coupled-receptor protein with 7 transmembrane domains... 

Targets with a clear association between a specific receptor or enzyme and an adverse effect are favored. For example, muscarinic... 

Highly correlated targets may be statistically associated with the same ADR. For example, tachycardia is mediated by blockade of the M2 muscarinic receptor, and is also found significantly associated to M2 data in BioPrint according to our statistical analysis (Fig. 4). However, since Mi... 

Of the different sensory modalities, olfaction does not appear to feature in reports of the effects of plant hallucinogens. Since olfaction is the one sense not relayed through the thalamus, this brain area is likely to be central to the changes in consciousness described. Many target receptors implicated, e.g. muscarinic, 5-HT2, D2, D3 and opiate, are present in this thalamic nuclei the human brain. 

Fig. 1. Schematic drawing of the cholinergic neurotransmission. In case of ganglionic and neuro-muscular synapses, the receptor is of the nicotinic, sodium channel-coupled type, in case of synapses at the parasympathetic target organs, the receptor is of the muscarinic, G-protein-coupled type. The predominant ehinination pathway of the transmitter acetylcholine...

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