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Centrally-Acting Muscle Relaxants
A heterogenous group of drugs acting in the CNS to reduce
skeletal muscle tone leading to therapeutic application in
treatment of spasticity and spasms
GABAB Receptor Agonist: Baclofen
2 Receptor Agonists: Tizanidine, clonidine
Tricyclic Antidepressants-related compounds: Cyclobenzaprine
(Flexeril)
Miscellaneous: Methocarbamol, Carisoprodol, and Orphenadrine
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GABAB Receptors
Metabotropic receptor (GPCR): Heterodimers composed of R1and R2
subunits.
Endogenous agonist: GABA
Present pre-synaptically and post-synaptically
Pre-synapse: Inhibition of Ca2+ entry Post-synapse: Stimulation
of K+ efflux
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Baclofen (Lioresal; oral, IT):
MOA: Selective GABAB receptor agonist
Therapeutic Use: Muscle Spasticity
Adverse Effects: Sedation, drowsiness, loss of motor
coordination, muscle weakness
Additive effect with other CNS depressants
Abrupt withdrawal reactions (IT baclofen): Hyperpyrexia,
rebound/increased spasticity, muscular rigidity and
rhabodmyolysis
Tolerance: Develop with use in chronic spasticity, attributed
to
receptor desensitization and downregulation of GABAB
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Sites of action of GABAB and 2 agonists
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Tizanidine (Zanaflex; oral):
MOA: Selective 2 receptor agonist decreases excitatory inputs
to
motor neurons Also inhibits nociceptive transmission in the
spinal cord dorsal horn
Therapeutic Uses: Spasticity
Adverse Effects:
Sedation, somnolence, drowsiness, visual hallucinations
Xerostomia
Hypotension, bradycardia
Asthenia: loss of strength, physical weakness
Abrupt withdrawal: Rebound hypertension, tachycardia and
hypertonia Comparative efficacy with clonidine: Similar efficacy
with
lesser risk of hypotension
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Spinal Cord
Raphi Nucleus
Descending
Serotonergic
neurons
Cyclobenzaprine (Flexeril;
oral):
MOA: 5-HT2 receptor antagonist
at the spinal level Alpha motor neuronal activity is
regulated by descending
serotonergic neurons from
medullary raphe
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Cyclobenzaprine:
Tricyclic Antidepressant-like effects: Inhibits NE re-uptake
Anticholinergic
Therapeutic Use:
Acute muscle spasms
Lower back pain, neck pain
Adverse Effects:
CNS: Drowsiness, sedation, dizziness
Xerostomia Potential for prolongation of cardiac conduction
time, arrhythmia, tachycardia
Combination with Monoamine oxidase inhibitors can lead to
hypertensive crisis,
convulsions
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Miscellaneous Central Muscle Relaxants Methocarbamol
(Robaxin),
Carisoprodol (Soma), Orphenadrine(Norflex)
MOA -Act centrally on the level of spinal cord to
depress polysynaptic neuron transmission
-Orphenadrine: central atropine-like
effects
-Causes CNS depression
Therapeutic Uses -Muscle spasms
-Muscle pain
-Tetanus: Methocarbamol
Adverse Effects Generally: sedation, drowsiness, additive
effects with other CNS depressantsMethocarbamol:
Bradycardia,
hypotension
Carisoprodol: Potential for abuse
Orphenadrine: Tachycardia, xerostomia
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Direct-acting Muscle Relaxants Botulinum Toxin (BoNT)
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Direct-acting Muscle Relaxants
Dantrolene
