Presented by,

Ved prakash panda

Roll no. 256216887010
M. Pharm (Pharmacology)
Malla Reddy college of pharmacy
1. INTRODUCTION
2. TYPES
3. SCREENING MODEL FOR CENTRALLY ACTING
MUSCLE RELAXANTS
4. SCREENING MODEL FOR PERIPHERALLY
ACTING MUSCLE RELAXANTS
 Skeletal muscle relaxants are drugs that act
peripherally at neuromuscular junction or
centrally in the cerebrospinal axis to reduce
muscle tone or cause paralysis.
 The term muscle relaxants is refer two major
therapeutic group:
1. Neuromuscular blockers ( acts peripherally)
2. Spasmolytics (acts centrally)
 Muscle relaxation & paralysis can occour by
interrupting function at motor end plate at
nicotinic cholinergic receptors.
 Normally, a neve impulse arrives at motor
nerve terminal, initiating an influx of calcium
ions, which cause the exocytosis of synaptic
vesicles containing acetylcholine.
 Acetylcholine then diffuses across the
synaptic cleft, it bind to the nicotinic
receptors located on the motor end plate.
 The binding of two Ach molecules results in
conformational changes in the receptor that
opens the sodium-potassium channel of the
nicotinic receptors.
 This allowa Na+ & ca++ ions to enter the cell
& k+ ions to leave the cell, causing a
depolarisation of the end plate, resulting in
muscle contraction.
 Most neuromuscular blockers functions by
blocking transmission at the end plate of the
neuromuscular junction.
 NEUROMUSCULAR BLOCKING AGENTS:
 NON DEPOLARIZING/ COMPETITIVE
BLOCKERS:
 D-tubocurarine, pancuronium,
vencuronium,mivacurium
 Depolarizing blockers:
 Succinylcholine, suxamethonium,
decamethonium
 DIRECTLY ACTING AGENTS:
 Dantroline sodium
 TUBERCURARINE, block the agonist, Ach
from binding to nicotinic receptors, there by
preventing depolarization.
 SUCCINYLCHOLINE, mimic Ach, but block
muscle contraction by prolong depolarisation
by acting on nicotine receptor.
 DANTROLENE, directly acts on,
RYR1(Ryanodine receptor) calcium channels
in the sarcoplasmic reticulum of skeletal
muscle & prevent ca++release. Thus prevent
contraction.
 These are drugs which reduce skeletal muscle
tone by a selective action in the cerebrospinal
axis, without altering consciousness.
 They selectively depress spinal & supra spinal
polysynaptic reflex involved in the regulation
of muscle tone.
 Drugs acting are:
1. Benzodiazepines- diazepam
2. GABA mimetics- baclofen, thiocolchicoside
3. Central alpha2 agonist- clonidine,tizanidine
 DIAZEPAM enhance the effect of inhibitory GABA
by binding to the benzodiazepine site on GABA a
receptor & include cl- influx & thus hyperpolarize
motor neurons.
 CLONIDINE act as alpha-2 agonists which acts on
the pre synaptic nerve fibre & dec. the ca++ions
influx there by decrease the neurotransmitter
release.
 BACLOFEN acts as GABA agonist at GABA b
receptors present in the brain & spinal cord
cause hyperpolarisation due to k+ conductance.
 BACLOFEN also inhibits the neural function
presynapyiclly by reducing ca++ influx & there
by decreases the neurotransmitter release in both
brain & spinal chord.
 IN VIVO MODELS:

1. Inclined plane test in mice

2. Chimney test in mice
3. Grip strength in mice
4. Rota rod test in mice
 PRINCIPLE:
The inclined plane method is used to assess
skeletal muscle relaxation .
 PROCEDURE:
 Male mice with a body weight between (20-30) gm are
used
 The plane consists of two rectangular plywood boards
connected at one end by a hinge. One board is the base,
the other is the movable inclined plane which is set at 65
degrees.
 The test compound or the standard is administered to
group of 10 mice either orally or parenterally. 30 min later
the mice are placed at upper part of the inclined plane &
given a cutoff time of 30 sec to hang on or fall off.
 The peak time is determined as the time at which a
compound produces the maximal performance deficit.
 PROCEDURE:
 Male mice weighing between 16-22 gm are
used
 Pyrex-glass cylinder 30 cm long are required.
 Initially the cylinder is held in a horizontal
position, at the end of cylinder near a 20 cm
mark from the base, a mouse is introduced
with the head forward.
 When mouse reaches the other end of the
cylinder, the tube is moved to a vertical
position.
 Immediately the mouse tries to climb
backwards & performs, coordinated
movement.
 The time required by the mouse to climb
backwards to top of the cylinder is noted.

 The ED50, the dose at which 50% of the

animals fail to climb backwards with in 30
sec. is calculated.
 Procedure:
 Male or female mice with an average weight
of 20 gm are used
 The animals are exposed to a horizontal thin
or metallic wire suspended about 30 cm into
the air which they immediately grap with the
forepaws
 The mouse is released to hang on with its
forelimbs, normal animals are able to catch
the threat with hind limb & climb on to it
within 5 sec.
 After oral or parenteral administration of
test/ Standard drugs the animals are tested
every 15 mins for 2 hrs.
 Animals which are not able to climb on to the
wire with hind limbs with in 5 sec or fall off
are considered to be impaired by drug effect.
 The disturbance of the grasping reflex can be
considered to be caused by central
relaxation.
 PRINCIPLE:
The test is used to evaluate the activity of
the drugs interfering with motor cordination &
muscle activity by testing their ability to remain
on a revolving rod.
 Procedure:
 Male swiss mice (20 – 30gm body weight ) are
used.
 The apparatus consists of a horizontal wooden
rod or metal rod coated with rubber with 3 cm
diameter to a motor with the speed adjusted to
200 rotations per minute.
 The rod is 75cm in length & is divided into 6
section by plastic disc, the rod is in a height of
about 50cm above the table top in order to
discourage the animals from jumping off the
roller
 Only those mice, which demonstrate their ability
to remain on the revolving rot for at least 60 sec
are chosen for the test.
 30 mins after I.P administration of tes/ stnd.
Drug the animals are placed on the rota rod for 1
min.
 The no. of animals falling within 1 min. are
counted, ED50 is determined at which 50%
animals fall from the rota rod.
 IN VIVO MODELS:

1. PHRENIC NERVE-DIAPHRAGM PREPARATION

2. SCIATIC NERVE –GASTROCENEMIUS MUSCLE
PREPARATION OF RABBIT.
3. THE RABBIT HEAD DROP METHODS.
 Male wistar rats weighing between 150 -
200gm are used.
 The animal is sacrificed & blood is fully
drained.
 The thorax is opened and the phrenic nerve is
cut below the thymus and a thread is tied to
the cut end another thread is tied to the
tendinus part of diaphragm.
 It is introduced into an organ bath and a
thread tied to the muscle is attached to a
force transducer.
 The organ bath contain tyrode solution and kept
oxygenated at 37degree C.
 The nerve is stimulated with a pair of electrodes,
it is stimulated at the rate of 12 times per minute
by wave pulse of 0.5 ms duration at 3-5 v.
 The contraction are recorded through a
transducer on a physiograph.
 The test drug are introduced in the organ bath
for a period of 5- 10 min. a wash out period of 5
min is given before the next dose is tried.
 The force of contraction after the addition of
graded doses of drugs is recorded & use for
establishing a DRC which is used to calculate
ED50 values.
 PROCEDURE:
 Rabbit weighing 1-2 kg are anesthetized with
200mg/kg of phenobarbital, administred slowly into
the marginal ear veins
 The sciatic nerve is identified, ligated & cut. An
electrode is placed on the peripheral portion of the
nerve.
 The twitched of muscle are elicited by stimulation &
are recorded through a force transducer on a
physograph.
 The force of contraction as recorded on the
physiograph after injection of the graded dose of test
and stnd. Drugs are compared with control responses
 Procedure:
 Rabbits of either sex weighing 2-3 kg are
used, they are placed in a comfortable
posture in the rabbit holder and the test &
standard drug is injected by slow intravenous
injection at the rate of 0.1ml/15 sec till the
muscles supporting the head become
sufficiently relaxed to prevent the head
remaining in the normal raised position.
 The falling of head is considered as the end
point & the I.V drip is stopped immediately.
 The volume of the drug solution injected till
the end point is noted and the amount of
drug administered is calculated.
 Injection of neostigmine is immediately given
to revive the strength of neck muscle &
prevent further damage.
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