The musculoskeletal system includes bones, muscles, cartilage, tendons, ligaments, and joints. There are three main types of muscles: cardiac, skeletal, and smooth. Neurotransmitters play a key role in mediating flexibility and rigidity in the musculoskeletal system by relaying signals between neurons. Baclofen and tolperisone are examples of centrally-acting muscle relaxants that decrease muscle tone by stimulating GABA receptors or inhibiting calcium and sodium channels. They are used to treat conditions involving muscle spasm, spasticity, and pain.

1. Prepared By
Muhammad Nizam Uddin
M.Pharm
Jahangirnagar University

2. Musculoskeletal system is made up of the body's
 Bones (the skeleton),
 Muscles,
 Cartilage,
 Tendon (a tough band of fibrous connective tissue
that usually connects muscle to bone and is
capable of withstanding tension)
 Ligaments (a tough band of fibrous connective tissue
connect bone to bone)
 Joints and
 Other connective tissue (the tissue that supports and
binds tissues and organs together)
MUSCULOSKELETAL SYSTEM

3. There are three types of muscles –
 Cardiac muscle
 Skeletal muscle and
 Smooth muscle
MUSCLES

4. Cardiac muscle is a type of involuntary
striated muscle found in the walls of the
heart, specifically the myocardium. Cardiac
muscle cells are known as cardiac
myocytes (or cardiomyocytes).
Skeletal muscle embedded with skeleton
generally contracts voluntarily (via somatic
nerve stimulation), although they can
contract involuntarily through reflexes.
Smooth (or visceral) muscle, forming the
muscle layers in the walls of the digestive
tract, bladder, various ducts, arteries and
veins, and other internal organs.
MUSCLES

5. Flexibility and rigidity is a very common
phenomena of musculoskeletal system in human
body. Neurotransmitters play the key role to
mediate that.
Neurotransmitters are chemicals that are used to
relay, amplify and modulate signals between a
neuron and another cell.
NEUROTRANSMITTER

6. NEUROTRANSMITTER:
EXCITATORY OR INHIBITORY
Some neurotransmitters are commonly described as
"excitatory" or "inhibitory".
The effect on the postsynaptic cell depends entirely on
the properties of the receptors. It so happens that for
some neurotransmitters (for example, glutamate), the
most important receptors all have excitatory effects: that
is, they increase the probability that the target cell will fire
an action potential.
For other neurotransmitters (such as GABA, glycine), the
most important receptors all have inhibitory effects.

7. Action potential
An action potential is a very rapid change in membrane
potential that occurs when a nerve cell membrane is
stimulated.
Specifically, the membrane potential goes from the
resting potential (typically -70 mV) to some positive
value (typically about +30 mV) in a very short period of
time (just a few milliseconds).

8. Action potential

9. Action potential

10.  Action Potential causes opening of calcium
channel in presynaptic nerve & then vesicle to
open
 Neurotransmitter released into synapse
 Locks onto receptor molecule in postsynaptic
membrane
NEUROTRANSMITTER RELEASE

11. NEURONAL TRANSMISSION

12. When neuronal transmission is impaired, hypertonicity,
spasm and spasticity of muscle takes place.
• Hypertonicity is an increased tension of the
muscles, meaning the muscle tone is
abnormally rigid, hampering proper
movement.
• Spasm is a sudden, involuntary contraction
of a muscle, a group of muscles
• Spasticity is sustained muscle spasm or
contractions or a condition in which certain
muscles are continuously contracted.

13. Muscle relaxant is a drug which affects skeletal
muscle function and decreases the muscle tone.
Muscle relaxants
Centrally acting muscle relaxant: Tolperisone, Baclofen
Direct acting muscle relaxant: Dantrolene

14. Baclofen

15. MODE OF ACTION
Baclofen is a GABA-B agonist which mimic the effect of GABA.
Baclofen inhibits both monosynaptic and polysynaptic
reflexes in both pre & postsynaptic mechanism by
stimulating the GABAB-receptors, which inhibits the
release of glutamate and aspartate.
Moreover, Baclofen
• Decreases calcium influx in presynaptic nerve
• Increases the concentration of glycine, another
potent inhibitory neurotransmitter.
Baclofen also exerts an anti nociceptive effect by
inhibiting substance P.

16. INDICATION
• Spasticity due to stroke, spinal cord injury
• Muscle spasm
• Muscular rigidity
• Low back pain
And
• Trigeminal neuralgia (Jaw and facial pain)
• Dysfunctional voiding (Urinary incontinence)
• Hiccup

17. Dosage and administration

18. Tolperisone Hydrochloride

19. MODE OF ACTION
Tolperisone suppresses mono- and poly-synaptic
reflex transmission by pre- and post-synaptic
mechanisms, especially in pathologically increased
reflexes.
Tolperisone
• inhibits voltage-gated Ca2+ channels. So
decreases neurtransmitter release.
• inhibits voltage-gated Na+ channels.
Hyperpolarizaiton takes place.
Tolperisone also increases the peripheral circulation
through vasodilatory action.

20. INDICATIONS
• Painful muscle spasm associated with disorders of the
locomotor system: Low back pain, sciatica,
osteroarthritis, rheumatoid arthritis, spondylosis
• Muscle spasticity associated with neurological
conditions: Stroke, spinal cord injury, multiple sclerosis,
cerebral palsy.
• Decreased peripheral circulation:
As seen in atherosclerosis, Raynaud’s disease, and
intermittent claudication.
• Rehabilitation: Treatment after limb fractures followed by
long-term fixation; post-operative therapy of
traumatological and orthopedic limb surgery; rehabilitation of
hemiplegic patients.

21. DOSAGE AND ADMINISTRATION
Adults:
The total daily dosage is 150-450mg, divided into 3 equal
doses, according to the individual requirement and
tolerance of the patient.
Children:
3 months to 6 years, 5-10 mg/kg/day divided into three
doses; 6 to 14 years, 4-12 mg/kg/day divided into three
doses.