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methylscopolamine review properties radioligand
Partial answer - given only as a comment.
(Note: A good radioligand binds to something of interest to
researchers.)
In this case, it is a good high affinity, saturable, radioligand for
muscarinic acetylcholine receptors.
The following citation should have more useful information.
Flynn, D.D. and Mash, D.C. Distinct kinetic binding properties of
N-[3H]-methylscopolamine afford differential labeling and localization
of M1, M2 and M3 muscarinic receptors in the primate brain. Synapse
14: 283 - 296, 1993.
However, by using pirenzepine instead of [3H]NMS, the binding
properties of the antagonist pirenzepine led to the initial
classification of muscarinic receptors.
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Molecular Biology, Pharmacology, and Brain Distribution of Subtypes of
the Muscarinic Receptor
Frederick J. Ehlert, William R. Roeske, and Henry I. Yamamura
http://www.acnp.org/g4/GN401000010/CH010.html
Perhaps the first time that strong pharmacological evidence for the
existence of subtypes of the muscarinic receptor appeared was in the
early 1980s when the novel binding properties of the selective
muscarinic antagonist pirenzepine were first described. This compound
had been in use in Europe as an antiulcer drug. Unlike other
muscarinic antagonists, it blocked gastric acid and pepsinogen
secretion at doses which had little or no influence on intestinal
motility, salivary secretions, and heart rate (56). It was shown
subsequently that pirenzepine bound with high affinity to a subclass
of the muscarinic receptor that was abundant in the cerebrum and in
peripheral ganglia, whereas it displayed intermediate binding affinity
for receptors in exocrine glands and low affinity for receptors in the
heart (34, 35). Pirenzepine was shown to block the pressor response to
McN-A-343 with high potency, whereas it only weakly antagonized the
bradycardia caused by vagal stimulation (35). In contrast, more
conventional muscarinic antagonists, such as N-methylscopolamine
(NMS), are approximately equipotent at blocking these two effects. A
variety of subsequent pharmacological experiments have demonstrated
that pirenzepine can be used to divide muscarinic receptors into the
same three classes mentioned above, namely, a major subtype in brain
and peripheral ganglia (high affinity for pirenzepine), a cardiac
subtype (low affinity for pirenzepine), and a subtype mediating
responses in exocrine glands and smooth muscle (intermediate affinity
for pirenzepine). These three subtypes of the muscarinic receptor are
known as M1, M2, and M3, respectively. A complete definition of
muscarinic receptor subtypes is given below
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The book is Basic Neurochemistry. Second link below. If the link
does not work, you can go to the first link and search for the book.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=books
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?query_key=9&db=books&dopt=&page=0&dispmax=20&WebEnv=0MHWzXECkLf2aIhTiYNVNDj5xTfzmwGgjXq1Qbxu9a_w80K20PwrAP&WebEnvRq=1&rid=bnchm.section.808#811
Unlike agonists, most muscarinic antagonists, such as
quinuclidinylbenzilate, N-methylscopolamine and atropine, bind to the
receptor with Hill slopes of unity, as expected for a mass-action
interaction with a single receptor type. There is little difference in
affinity for these ligands in various tissues. Similar findings with
other antagonists initially suggested that all muscarinic receptors
were the same. However, a number of functional studies have suggested
that muscarinic receptors are heterogeneous, and several putative
subtype-selective antagonists have been described throughout the
years.
Pirenzepine binds to muscarinic receptors in cortex, hippocampus and
ganglia with relatively high affinity; these sites have been termed
M1, as mentioned earlier. Heart, gland and smooth muscle muscarinic
receptors, as well as those in brainstem, cerebellum and thalamus,
show 30- to 50-fold lower affinity for PZ The affinity for classic
antagonists like N-methylscopolamine is the same in all of these
regions, emphasizing the unique selectivity of PZ. |
