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Old 04-24-2011
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Drug Confusion about the mechanism of aciton of Morphin

I have a confusion about the MOA of the opioid analgesics. OK, I know they act through Gi coupling by inhibiting pre and postsynaptic nerves.with their mu, kappa and delta receptors.
but i also know that the muscarinics receptors are universal, if u activate one, u stimulate all of them and vice versa.
so how can morphine have muscarinic effect causing MIOSIS and also have anti-muscarinic effects like decrease peristalsis, constipation, urinary retention?
I'm not clear. If u do, please help.

thanks.
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Old 04-24-2011
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Opioid drugs don't act on muscarinic receptors even though they have muscarinic like activities - at least not primarily so. This is just like if you use a muscarinic antagonist you're not going to feel relief from pain.

Morphine and other prototypical opioid receptor antagonists work on mu, kappa and delta receptors mainly - some of these receptors have downstream Gi effects, but some do other things. I don't think you're supposed to connect the two.

I might be confused here more than you - but your question's got me thinking... Anyone else?
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Old 04-24-2011
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thank you
i think that the only thing i can do is to just accept it just the way it is.b/c when i think about the opiods they are not conventional in that they are multiple effects a little bit contradictory,like respiratory depression that does not responde to Oxygen but to naloxone,the antitussive action which nobody know how or why b/c it's not mu mediated,and i think that the opioids are the only group of drugs with a mixed agonist-antagonist action stimulating the kappa and blocking the mu at the same time.

i just accept it and study it cold.
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Old 04-24-2011
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I agree - I think thats the best thing to do... It is a little confusing because like you say - the effects aren't all sympathetic type or parasympathetic type but I guess the idea is to think of it as mostly a mu based pain signal drug with associated side effects. I researched this a little before I answered your question and it looks like there is still quite a bit of research left to do on exactly how opioids work.
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Old 04-25-2011
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thank you so much ashishkabir.
i was thinking that i did not understand well something or that i mixed something that i should not.

i don't know if it's me but have you ever think about this,another contradiction that we can't do nothing about.
you know that beta 2 is an epinefrine receptor and epinefrine almost always do what glucagon does.but how can this same epinefrine stimulates glycogenolysis to increase glucose and at same time increases insulin secretion which stimulates glycogen synthesis
and decrease glucose through the same beta 2 receptor.
thank you again,now i can move on in peace.
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