1. Awatif B. Al-Backer

2. Stimulants & their Blockers 1-Drugs acting on Nn R Agonist -Dil. Nicotine (0.01%, 0.1ml) -MOA: Dil. Nicotine stimulates Gs protein in cell membrane → activates Na-channels → rapid ↑ intracellular Na → depolarization and AP → contraction Antagonist Antagonist -Conc. Nicotine (0.1%, 0.1ml) -Conc. Nicotine is depolarizing ganglionic blocker -MOA: it causes an initial depolarization (↑cont.) followed by excessive depolarization → transmission failure & muscular fatigue (exhaustion of the receptors)

3. Awatif B. Al-Backer Stimulants & their Blockers 2-Drugs acting on M3 R Agonist -Ach (0.01%, 0.1ml) -MOA :Ach stimulates M3R → ++ Phospholipase C → Hydrolysis of (PIP2) into: 1- DAG → ↑opening of Calcium channels 2- IP3 → mobilization of cal. from its stores * Finally 1 & 2 leading to ↑ intracellular calcium→contraction Antagonist -Atropine (0.1ml, 0.1%) -It is a specific, nonselective, reversible, competitive blocker of M 3 R

4. Awatif B. Al-Backer Determination of The Site of Action of Unknown Using Isolated Rabbit Intestine Unknown Agonist Blocker + Agonist + Unknown Without washing w W

5. Awatif B. Al-Backer Experiment design Keys: N: normal myogenic contraction(1min.) Unk.: the unknown drug(0.1ml, 30sec.) DN: diluted nicotine (0.1ml, 30sec.) CN: concentrated nicotine (0.1ml) Ach: acetylcholine (0.1ml, 30sec.) At.: atropine (0.1ml) N Unk N DN N CN N DN Unk N Ach N At Ach Unk