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

GABAB Receptors
Metabotropic receptor (GPCR): Heterodimers composed of R1 and R2 subunits. Endogenous agonist: GABA Present pre-synaptically and post-synaptically Pre-synapse: Inhibition of Ca2+ entry Post-synapse: Stimulation of K+ efflux

 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

Sites of action of GABAB and 2 agonists

 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

 Cyclobenzaprine oral):
Raphi Nucleus

(Flexeril;

Descending Serotonergic neurons

MOA: 5-HT2 receptor antagonist at the spinal level Alpha motor neuronal activity is regulated by descending serotonergic neurons from medullary raphe

Spinal Cord

 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

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 -Muscle spasms -Muscle pain -Tetanus: Methocarbamol
Generally: sedation, drowsiness, additive effects with other CNS depressants Methocarbamol: Bradycardia, hypotension Carisoprodol: Potential for abuse Orphenadrine: Tachycardia, xerostomia

Therapeutic Uses

Adverse Effects

Direct-acting Muscle Relaxants

Botulinum Toxin (BoNT)

Direct-acting Muscle Relaxants

Dantrolene