351 PHL 5 th Lecture Dose Responce Curve of Ach & The Drugs Acting on The Frog Rectus Abdominis

Neuromuscular (myoneural) Frog Rectus Abdominis Description: It is a skeletal, voluntary, striated & transverse muscle It receives somatic motor innervation The transmission is mediated through release of Ach that acts on Nm Rs present postsynaptically on the muscle Neuromuscular (myoneural) junction CNS Voluntary motor nerve Nm R

Neuromuscular transmission 1- Action potential propagation through nerve fiber 2- Calcium influx into the nerve ending 3- Release of Ach from its vesicles (fusion with membrane & exocytosis) 4- Release of Ach into synaptic cleft 5- Ach binds to Nm R postsynaptically 6- Activation of Na-K channels→ Na influx; contraction 7- Ach action is terminated by cholinesterase enzyme

Comparison between Nn & Nm smooth muscle skeletal muscle Located in ganglia Located postsynaptically(MEP)

Drugs acting on skeletal muscles 1- Centrally acting drugs: e.g. Diazepam (skeletal ms. relaxant) 2- Peripherally acting drugs: a- Presynaptically (motor nerve) b- Postsynaptically (sk.ms.)

Presynaptically acting drugs Continue Presynaptically acting drugs 1- Inhibit AP propagation: e.x. local anesthetics 2- ↓ Ach synthesis: e.x. hemicholinium, triethylcholine 3- ↓ Ach release: e.x. botulinum toxin 4- ↓ calcium conc.: e.x. Magnesium

Continue Postsynaptically acting drugs: A-Drugs that decrease transmission ( Ach release) B-Drugs that increase transmission

Drugs that affect skeletal muscles; cont. Drugs that decrease transmission: Types Non-depolarizing (Competitive) Depolarizing (noncompetitive) MOA Competing with Ach at NmR Initial depolarization followed by persistence depolarization→ muscle fatigue transmission failure & receptor blockage Examples Tubocurarine Gallamine Succinylcholine Decamethonium Type of paralysis produced Flaccid Spastic

Continue Drugs that increase transmission:- Cholinesterase inhibitors: A- Reversible e.g. neostigmine, physiostigmine B- Irreversible e.g. organophosphorus insecticides * Both will lead to accumulation of Ach at myoneural junction

PART 1 Height = A-B Awatif B. Al-Backer A N W+N W+N W+N W+N 0.05 ml 0.1 ml 0.2 ml 0.4 ml Ach Ach Ach Ach Height = A-B Awatif B. Al-Backer

PART 2 Awatif B. Al-Backer N W+N W+N W+N 0.1 ml 0.1 ml 0.1 ml 0.2 ml 0.1 ml Ach Ach Ach Curare Ach 0.1 physiostigmine Awatif B. Al-Backer

Curves On semi-log paper On normal paper Ht. * Ht. * * Dose Dose