Living Textbook MC 417

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Skeletal Muscle Relaxants

Spasticity

Spasticity is an increase in tonic stretch reflexes and flexor muscle spasms together with muscle weakness, often involving abnormal function of bowel, bladder and skeletal muscle.  Mechanisms involve the stretch reflex arc itself and higher centers in CNS, so pharmacologic therapy may modify arc by interfering directly with skeletal muscle, by reducing hyperactive fibers that excite primary motoneuron and enhance activity of inhibitory interneurons.

Examples of Spasmolytic Agents:

Baclofen (Lioresal®); Top 200 is an agonist at the GABAA receptor, that causes hyperpolarization, likely by increased K+ conductance, and likely reduce release of excitatory transmitters.  It has less sedative effects than diazepam and does not reduce overall muscle strength.

Baclofen is given intrathecally and does not leave spinal cord, reducing peripheral symptoms or orally for intractable low back pain.

Tizanidine (Zanaflex®) is an α2-adrenergic receptor agonist that is used at doses that causes fewer cardiovascular effects than clonidine and lower effect on blood pressure.   It does not cause much loss of muscle weakness, but does cause drowsiness, hypotension, dizziness, dry mouth, hepatotoxicity.

It is effective for management of migraine

Dantrolene (Dantrium®) is a hydantoin derivative that interferes with excitation contraction coupling in muscle fibers and the release of activator calcium through the ryanodine receptor (RyR) channel, a calcium channel.   Dantrolene binds to the RyR channel and blocks opening of the channel.

Main adverse effects: muscle weakness and sedation and is used to treat malignant hyperthermia.

Gabapentin (Neurintin®); Top 200 and Progabide (Gabrene®) are GABAA and GABAB agonist that also act on the high voltage-activated Ca2+ channel.

 

Glycine is an inhibitory neurotransmitter that could have spasmolytic activity.

Idrocilamide (Talval®) and Riluzole (Rilutek®) are used in the treatment of amyotrophic lateral sclerosis, have spasm-reducing effects, inhibiting glutamate release and blocks NMDA receptors.

Botulinum toxins are useful for generalized spastic disorders (cerebral palsy).  Benefits persist for weeks to months.

The three Top 200 agents: Carisoprodol (Soma®), Cyclobenzaprine (Amrix®, Flexeril®) and Methocarbamol (Robaxin®) are newer muscle relaxants, the exact mechanism is not known.  Cyclobenzaprine is a tricyclic structure that shows antimuscarinic effects.  It is metabolized by CYP450.