‫بسم هللا الر حمن الر حيم‬

The effect of drugs on the isolated

frog rectus abdominis muscle
 Objectives
 Describe frog rectus abdominis muscle
 Discuss neuromuscular transmission
 Describe Nicotinic receptors (NN and NM
receptors)
 Explain drugs acting on neuromuscular
transmission
 Drugs affecting skeletal muscles
I- Centrally acting drugs
e.g. Diazepam (spasmolytic agent)
II- Peripherally acting drugs (At NMJ)
A- Presynaptically (motor nerve)
B- Postsynaptically (Motor end-plate of
skeletal muscle)
C- Directly acting on the muscle
Drugs affecting skeletal muscles (Cont.)
A. Presynaptically acting drugs
& Cause muscle relaxation.
1- Decrease Acetylcholine Synthesis
e.g. Hemicholinium
2- Decrease Acetylcholine Release
e.g. Botulinum toxin
 Drugs affecting skeletal muscles (Cont.)
B. Postsynaptically acting drugs
1- Drugs that increase transmission at NMJ &
cause muscle contraction
2- Drugs that decrease transmission at NMJ &
cause muscle relaxation
C. Drugs directly acting on the muscle
 A. Drugs that increase transmission
Cholinesterase inhibitors
Increase Acetylcholine at neuromuscular junction
a- Reversible
Neostigmine (Intermediate acting):
• Used in reversing muscle relaxation caused by non-
depolarizing muscle relaxants (e.g. Atracurium)
• Used in treatment of Myasthenia gravis.
Edrophonium (Short acting):
• Used for diagnosis of Myasthenia gravis
• Used to differentiate Myasthenia/Cholinergic crisis
 A. Drugs that increase transmission
(Cont.)
b- Irreversible
• e.g. Organophosphorous compounds
• Used as insecticide poisoning
 B. Drugs that decrease transmission
a. Non-depolarizing (Competitive) muscle
relaxants:
e.g. Atracurium & Pancuronium
b. Depolarizing (Non-competitive) muscle
relaxant:
e.g. Succinylcholine
These drugs are mainly used during surgery
along with general anesthetics to relax skeletal
muscle.
C. Drugs that act directly on the muscle
• Dantrolene
• Decreae release of calcium from the
sarcoplasmic reticulum of the muscle and
cause muscle relaxation,
• Used to treat muscle spasm in Malignant
Hyperthermia
 Frog Rectus Abdominis Muscle
Description:
- It is a skeletal, voluntary, striated muscle
- Receives somatic motor innervation
- Transmission is mediated through release of
Acetylcholine (Ach) that acts on Nicotinic receptors (Nm
receptors) present postsynaptically on motor-end plate of
muscle
Neuromuscular
junction
CNS
Motor nerve
Ach
Nm Receptor Skeletal
Motor-end plate muscle
Neuromuscular transmission
 Neuromuscular transmission
1- Nerve impulse coming from CNS to motor
nerve terminal
2- Release of Ach from vesicles in motor nerve
terminal to synaptic cleft
3- Ach binds to Nm Receptor post-synaptically
4- Activation of Na channels, influx of Na at
motor end plate & generation of action
potential, which extends to entire muscle
5- Calcium release from sarcoplasmic
reticulum and results in muscular contraction
6- Ach is rapidly metabolized by cholinesterase
enzyme
Location of Nicotinic receptors

Nn Nm

Autonomic skeletal muscle

ganglia
Requirements for Experiment
 Frog-ringer solution:
(Ca , K , PO4, Na , HCO3 &
Glucose)
Room Temperature (25 0C)
Frog is cold blooded animal.
 Procedure
• Draw a dose-response curve for action of Ach
on muscle
• Add 0.1ml of Ach, record contraction, wash
• Add 0.2ml of Ach, record contraction, wash
• Add 0.4ml of Ach, record contraction, wash
• Add 0.8ml of Ach, record contraction, wash
• Add 1.6ml of Ach, record contraction, wash
 Action of different doses (Gradually
increasing doses) of Acetylcholine on
skeletal muscle

0.1 ml 0.2 ml 0.4 ml 0.8 ml 1.6 ml

of Ach of Ach of Ach of Ach of Ach
 Procedure (Cont.)
1. Add 0.4ml of Ach, record contraction, wash
2. Add 0.4ml Atracurium, wait for 2 min. then, add
0.4 ml Ach , record contraction, wash
3. Add 0.4ml Atracurium, wait for 2 min. then, add
0.8 ml Ach, record contraction, wash
4. Add 0.4ml Atracurium, wait for 2 min. then, add
1.6 ml Ach , record contraction, wash
5. Add 0.4ml Atracurium, wait for 2 min. then, add
3.2 ml Ach , record contraction, wash
6. Add 0.4ml Atracurium, wait for 2 min. then, add
6.4 ml Ach , record contraction, wash
Action of different doses of Acetylcholine on skeletal
muscle in the presence of competitive antagonist
(Atracurium)
Higher doses of Ach have overcome action of Atracurium

0.4 ml 0.8 ml 3.2 ml 6.4 ml

of ach of ach of ach of ach
0.4 ml 1.6 ml
of ach of ach
Dose response of acetylcholine alone and with
competitive antagonist
• Competitive antagonist causes rightward shift
of dose response curve.