Tizanidine is an alpha-2 adrenergic agonist used for the management of muscle spasm, which may result from the effects of multiple sclerosis, stroke, an acquired brain injury, or a spinal cord injury. Spasticity is an increase in muscle accompanied by uncontrolled, repetitive contractions of skeletal muscles which are involuntary. Activation of alpha-2 adrenergic receptors on the presynaptic spinal motor neurons lead to the activation of Gi signaling cascade. This inhibits adenylyl cyclase and inactivates protein kinase A, thus decreasing calcium ion entry into the cell. Calcium in the cell is responsible for triggering the release of excitatory neurotransmitters such as glutamate (and aspartate) into the synapse. Glutamate acts on AMPA and NMDA receptors on the post synaptic motor neurons. Activation of AMPA receptors causes the influx of sodium in the post synaptic neuron. Activation of NMDA receptors causes an influx of calcium into the post synaptic neuron. The influx of positive ions in the cytosol causing depolarization of the motor neurons which then transmits a signal to muscle, causing muscle contraction/excitation. With reduced calcium entry in the presynaptic neuron, glutamate release is inhibited and less NMDA and AMPA receptors are activated, preventing depolarization of motor neurons and decreasing muscle contractions and spasms. Common adverse effects of taking tizanidine include drowsiness, blurred vision, dry mouth, weakness, constipation, nervousness, dizziness, hallucinations, dyskinesia, rhinitis.

Tizanidine References