The relative selectivity of anticholinergic drugs for the M1 and M2 muscarinic receptor subtypes
Identifieur interne : 006665 ( Main/Exploration ); précédent : 006664; suivant : 006666The relative selectivity of anticholinergic drugs for the M1 and M2 muscarinic receptor subtypes
Auteurs : Burke [États-Unis]Source :
- Movement Disorders [ 0885-3185 ] ; 1986.
English descriptors
- KwdEn :
- MESH :
- chemical , antagonists & inhibitors : Quinuclidinyl Benzilate.
- chemical , drug effects : Receptors, Muscarinic.
- chemical , pharmacology : Parasympatholytics, Phenothiazines, Pirenzepine.
- drug effects : Brain.
- Animals, Male, Rats, Rats, Inbred Strains.
Abstract
Anticholinergic drugs are used to treat a number of neurologic disorders, including parkinsonism, vestibular disturbances, and dystonia. Traditionally, these drugs have been thought to act in similar fashion, as competitive antagonists at a single class of muscarinic receptors, and not to differ significantly in their therapeutic efficacy. Recently, however, pharmacologic studies have shown that the novel antagonist pirenzepine is capable of recognizing heterogeneity among muscarinic receptors; high‐affinity pirenzepine sites have been classified as M1 sites and low‐affinity sites as M2. This study examined whether the anticholinergics currently available for treatment of neurologic symptoms have selectivity for these subtypes and whether they differ in their degree of selectivity; the study showed that these drugs do demonstrate selectivity. All had greater affinity for the M1 site, indicated by higher affinity for rat forebrain membranes, where M1 predominates, than hindbrain preparations, where M2 predominates. The degree of selectivity varied greatly; some compounds, such as ethopropazine, had little M1 selectivity, whereas others, such as scopolamine, trihexyphenidyl, and biperiden, were quite selective, like pirenzepine. It is unknown whether these differences in selectivity have any immediate therapeutic implications. However, these results support the emerging concept of muscarinic receptor subtypes and the prospect of developing more selective agents, with enhanced therapeutic efficacy.
Url:
DOI: 10.1002/mds.870010208
Affiliations:
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Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="1986">1986</date><biblScope unit="vol">1</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="135">135</biblScope><biblScope unit="page" to="144">144</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">80F5F1D0C49D7B1EDD78B0A09E3D0D8DBE6C0792</idno><idno type="DOI">10.1002/mds.870010208</idno><idno type="ArticleID">MDS870010208</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Anticholinergic</term><term>Brain (drug effects)</term><term>Male</term><term>Muscarinic</term><term>Parasympatholytics (pharmacology)</term><term>Phenothiazines (pharmacology)</term><term>Pirenzepine (pharmacology)</term><term>Quinuclidinyl Benzilate (antagonists & inhibitors)</term><term>Rats</term><term>Rats, Inbred Strains</term><term>Receptor</term><term>Receptors, Muscarinic (drug effects)</term><term>Subtypes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Quinuclidinyl Benzilate</term></keywords><keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>Receptors, Muscarinic</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Parasympatholytics</term><term>Phenothiazines</term><term>Pirenzepine</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Brain</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Male</term><term>Rats</term><term>Rats, Inbred Strains</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Anticholinergic drugs are used to treat a number of neurologic disorders, including parkinsonism, vestibular disturbances, and dystonia. Traditionally, these drugs have been thought to act in similar fashion, as competitive antagonists at a single class of muscarinic receptors, and not to differ significantly in their therapeutic efficacy. Recently, however, pharmacologic studies have shown that the novel antagonist pirenzepine is capable of recognizing heterogeneity among muscarinic receptors; high‐affinity pirenzepine sites have been classified as M1 sites and low‐affinity sites as M2. This study examined whether the anticholinergics currently available for treatment of neurologic symptoms have selectivity for these subtypes and whether they differ in their degree of selectivity; the study showed that these drugs do demonstrate selectivity. All had greater affinity for the M1 site, indicated by higher affinity for rat forebrain membranes, where M1 predominates, than hindbrain preparations, where M2 predominates. The degree of selectivity varied greatly; some compounds, such as ethopropazine, had little M1 selectivity, whereas others, such as scopolamine, trihexyphenidyl, and biperiden, were quite selective, like pirenzepine. It is unknown whether these differences in selectivity have any immediate therapeutic implications. However, these results support the emerging concept of muscarinic receptor subtypes and the prospect of developing more selective agents, with enhanced therapeutic efficacy.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>État de New York</li></region><settlement><li>New York</li></settlement><orgName><li>Université Columbia</li></orgName></list><tree><country name="États-Unis"><region name="État de New York"><name sortKey="Burke" sort="Burke" uniqKey="Burke" last="Burke">Burke</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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