1. 351 PHL
5 th Lecture
Dose Responce Curve of Ach & The Drugs Acting on The Frog Rectus Abdominis

2. 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

3. 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

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

5. 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.)

6. 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

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

8. 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

9. 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

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

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

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