Centrally acting muscle relaxants work by enhancing the inhibitory neurotransmitter GABA in the central nervous system to reduce muscle tone and spasms. There are several types of centrally acting muscle relaxants that work through GABA receptors or calcium channels, including diazepam, tizanidine, baclofen, and dantrolene. These drugs can be used to treat various muscle spasms and spasticity conditions.

1. Centrally acting muscle Relaxants
Dr. Johan

2. Muscle Relaxants
Learning objectives:
 what is a muscle relaxant
Various types of centrally acting muscle
relaxants
How do they act
Where they can be used

3. Definition
 Muscle relaxant is a drug which
affects skeletal muscle function and decreases
the muscle tone. It may be used to alleviate
symptoms such as muscle spasms, sprains &
pain
Muscle relaxants are of two major therapeutic
groups: neuromuscular blockers
and spasmolytics

4. Spasmolytics
Spasmolytics are used to alleviate
musculoskeletal pain, spasms and to
reduce spasticity in a variety of neurological
conditions. They are of three types
Centrally acting
Directly acting
Miscellaneous

5. Can you tell what is spasm and
what is spasticity

6. Mechanism of centrally acting drugs
Spasmolytic agents generally work by either
enhancing the level of inhibition, or reducing the
level of excitation.
Inhibition is enhanced by mimicking or enhancing
the actions of endogenous inhibitory substances,
such as gamma-Aminobutyric acid (GABA).
GABA is the chief inhibitory neurotransmitter in
the mammalian central nervous system.
In humans, GABA is directly responsible for the
regulation of muscle tone.

7. Individual centrally acting drugs
Diazepam
– Facilitating the action of -aminobutyric acid (GABA)
– Acts at all GABAA synapses
– Useful in muscle spasms of any origin
– sedation limits use
Tizanidine
-Alpha2 adrenoceptor agonist reinforces both pre and
post synaptic inhibition in the cord also inhibits
nociceptive transmission in the spinal dorsal horn
ADR: Drowsiness, hypotension, dry mouth

8. Baclofen
– GABAB agonist
– Induce hyperpolarization  serve as presynaptic
inhibitory function
– Toxicity: drowsiness, seizure activity
– Intrathecal administration effective in sever
spasticity.

9. Other centrally acting drugs used for local
muscle spasm
• Carisoprodol
• Chlorophenesin
• Chlorzoxone
• Cyclobezaprine
• Metaxalone
• Methocarbamol
• orphenadrine
•Most of them act as sedative at level of the spinal cord or brain
stem
•The main therapeutic use is in relief of acute temporary muscle
spasm cause by Local trauma or strain

10. DANTROLENE- directly acting SMR
• Prevents calcium release from the
sarcoplasmic reticulum through the ryanodine
receptors (RyR1) channel.
• Used orally reduces spasticity in UMN
disorders, hemiplegia, paraplegia, cerebral
palsy and multiple sclerosis.
• ADR: generalized muscle weakness, sedation
and occasionally hepatitis.

11. Malignant hyperthermia
 Triggered by GAs and Sch
 Sudden and prolonged release of calcium with
massive muscle contraction, lactic acid production
and increased body temperature.
 Prompt treatment by cooling the body and
bicarbonate infusion for correcting acidosis is
essential
 IV dantrolene is the drug of choice to reduce calcium
load

12. Miscellaneous
BOTULINUM TOXIN (BOTOX)
Mechanism of Action: blocks release of ACh in the
neuromuscular junction
Indications: spasticity, hyperhidrosis (excess sweating),
reduce facial lines and wrinkles
• Administration: subdermal injection
• Localized muscle paralysis occurs, so lines and
wrinkles are less apparent
• Effects lasts weeks to months

13. Other spasmolytics
 Gabapentin – antiepileptic drug
GABAB receptor agonist
multiple sclerosis
Progabide - a GABAA and GABAB agonist
Glycine – inhibitory aminoacid
neurotransmitter given orally and readily cross
the BBB. Tried in ALS and myotonia congenita.

14. Idrocilamide and Riluzole – newer drugs –
amyotrophic lateral sclerosis – through
inhibition of glutaminergic transmission in the
CNS
Thiocolchicoside & Tolperisone – GABAA
receptor agonist
used in painful spasm, mainly LBA & sports
injuries.

15. Thank you