1 / 13

Action Potential

a. b. a. Action Potential. Pharmacologic manipulation of the cholinergic system. Ca 2+. Na +. Muscarinic Receptor. ACH. Choline Acetyltransferase. Acetylcholinesterase. Acetyl CoA +. Acetylcholine. Choline. Na +. H +. Nicotinic Receptor. ACH. Choline. Acetate. Choline.

sakina
Télécharger la présentation

Action Potential

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. a b a Action Potential Pharmacologic manipulation of the cholinergic system Ca2+ Na+ Muscarinic Receptor ACH Choline Acetyltransferase Acetylcholinesterase Acetyl CoA + Acetylcholine Choline Na+ H+ Nicotinic Receptor ACH Choline Acetate Choline Presynaptic neuron Postsynaptic target

  2. O O C H C H 3 3 C C H C H N C H C C H C H N 2 2 3 2 2 H C O O 3 C H 3 A c e t y l c h o l i n e ( M i o c h o l ) O C H C H 3 3 C C H C H N C H 2 3 H N O 2 C H 3 B e t h a n e c h o l ( U r e c h o l i n e ) Direct acting cholinergic receptor agonists:Esters C H 3 H N 2 C H 3 C a r b a c h o l ( I s o p t o c a r b a c h o l ) O C H C H 3 3 C C H C H N C H 2 3 H C O 3 C H 3 M e t h a c h o l i n e (Provocholine)

  3. Direct acting cholinergic receptor agonists:Alkaloids and synthetic analogs H N ( C H ) 3 3 H O H C 3 O H H ( + ) - M u s c a r i n e C H H C H C 3 3 2 N C H 2 O N N O P i l o c a r p i n e C H 3 ( I s o p t o c a r p i n e ) N N i c o t i n e ( N i c o r e t t e )

  4. NH 3 Phospho - (+) G lipase C q PIP 2 IP Diacylglycerol COOH 3 2+ Increase Ca Activate Protein Kinase C Response Receptor agonists activate signal transduction pathways O C H 3 C C H C H N C H 2 2 3 C H O 3 C H Acetylcholine 3 M3 muscarinic receptor

  5. Molecular actions of acetylcholineat muscarinic receptors VI Tyr381 I VII Thr189 V II IV III Asp105

  6. Stereochemistry of cholinergic drugs Acetylcholine + + trans cis

  7. Stereochemistry of cholinergic drugs H N ( C H ) N ( C H ) 3 3 3 3 H C H C H O 3 3 H C 3 O O O H H H (+)-muscarine (+)-methacholine N ( C H ) 3 3 H H C 3 O O C H 3 (-)-methacholine

  8. Stereochemistry of cholinergic drugs N H H N ( C H ) N 3 3 H O H C H C 3 3 O O O H H (+)-muscarine Protonated pilocarpine

  9. Stereochemistry of cholinergic drugs (+)-muscarine Protonated pilocarpine

  10. Nicotine pKa 6.16 • Dibasic • Nicotinic receptors less stereoselective pKa 10.96

  11. Varenicline tartrate (Chantix) • 42 Nicotinic receptor partial agonist • Activates nicotinic receptor much less than nicotine; Blocks nicotine from binding • Well tolerated • Side effects: • GI related (nausea, constipation, gas, vomiting) • Altered dreams

  12. Clinical pharmacology of cholinergic receptor agonists Cholinesterase Drug Receptor Sensitivity Clinical Use Acetylcholine M, N Yes Intraocular use for miosis during surgery Carbachol M, N No Intraocular use for miosis during surgery, glaucoma Pilocarpine M No Glaucoma Bethanechol M No Urinary retention, post-operative ileus Varenicline N No Smoking cessation M=Muscarinic N=Nicotinic Why are antimuscarinic drugs contraindicated in glaucoma?

More Related