7.11:
Spasmolytic Agents: Chemical Classification
Spasmolytics are drugs that relieve spasticity, a condition marked by involuntary muscle contractions, muscle stiffness, weakness and painful muscle spasms.
Some spasmolytics are centrally acting and affect the spinal cord, while others are direct agents that work on the skeletal muscle cells.
Chemically, centrally acting spasmolytics can be of three types.
An ɑ2-agonist like tizanidine binds the ɑ2-adrenoceptor and inhibits the release of the excitatory neurotransmitter glutamate. It also promotes the release of glycine, which causes an influx of chloride into postsynaptic neurons, and reduces their excitability.
Ɣ aminobutyric acid or GABA mimetics like baclofen activate the GABAB receptors, inducing hyperpolarization of neuronal membranes and reducing their excitability.
They also inhibit the release of excitatory neurotransmitters and inactivate sensory, motor and interneurons.
The last group of spasmolytics includes the benzodiazepines such as diazepam, which binds the allosteric site of GABAA receptors and causes an influx of chloride ions, hyperpolarizing the membrane to inhibit neurotransmission.
7.11:
Spasmolytic Agents: Chemical Classification
Spasmolytic agents are drugs used to alleviate muscle spasms and spasticity. They can be categorized into different chemical groups based on their mechanisms of action. Centrally acting spasmolytics primarily affect the spinal cord, while others directly target skeletal muscle cells.
A major class of centrally acting spasmolytics is the α2-agonist, such as tizanidine. These drugs bind to α2-adrenoceptors, inhibiting the release of the excitatory neurotransmitter glutamate. They also promote glycine release, increasing chloride influx into postsynaptic neurons and reducing excitability.
GABA mimetics, such as baclofen, activate GABAB receptors, leading to hyperpolarization of neuronal membranes and reduced excitability. Baclofen suppresses the release of excitatory transmitters in the brain and spinal cord, suppressing sensory afferents, interneurons, and motor neurons.
Benzodiazepines like diazepam bind to the allosteric site of GABAA receptors and facilitate GABA's action in the CNS. Diazepam reduces spasticity, particularly in the spinal cord, but sedation can occur at doses required to reduce muscle tone.