From the Guidelines
Baclofen acts as a GABA-B receptor agonist in the central nervous system, reducing muscle tone and spasticity by inhibiting the release of excitatory neurotransmitters and hyperpolarizing neurons. The mechanism of action of baclofen involves binding to GABA-B receptors on presynaptic terminals and postsynaptic neurons in the spinal cord and brain, mimicking the inhibitory neurotransmitter GABA 1. This binding leads to hyperpolarization of neurons by increasing potassium conductance, which reduces the excitability of neurons. Additionally, baclofen inhibits the release of excitatory neurotransmitters like glutamate and aspartate by decreasing calcium influx into presynaptic terminals.
Key Points
- Baclofen is a GABA-B receptor agonist that reduces muscle tone and spasticity
- It binds to GABA-B receptors in the spinal cord and brain, mimicking the inhibitory neurotransmitter GABA
- Baclofen inhibits the release of excitatory neurotransmitters and hyperpolarizes neurons, reducing neuronal excitability
- It is effective for treating spasticity associated with spinal cord injuries, multiple sclerosis, and other neurological disorders
The provided evidence from the studies 1 supports the use of baclofen for treating spasticity, although it notes that oral baclofen may cause significant sedation and have less impact on spasticity in stroke victims compared to other disease conditions. However, the mechanism of action of baclofen remains the same, involving its agonist activity at GABA-B receptors. The therapeutic profile of baclofen, with its selectivity for GABA-B receptors, provides a unique approach to managing muscle spasticity with different side effect patterns compared to other medications like benzodiazepines.
From the FDA Drug Label
The precise mechanism of action of baclofen is not fully known. Baclofen is capable of inhibiting both monosynaptic and polysynaptic reflexes at the spinal level, possibly by hyperpolarization of afferent terminals, although actions at supraspinal sites may also occur and contribute to its clinical effect The mode of action of baclofen is not fully known. It is capable of inhibiting reflexes at the spinal level by possibly hyperpolarizing afferent terminals. Actions at supraspinal sites may also contribute to its clinical effect 2
From the Research
Mode of Action of Baclofen
The mode of action of baclofen is primarily associated with its role as a GABA(B) receptor agonist. This is evident in its ability to treat spasticity, a condition characterized by excessive contraction of the muscles and hyperflexia in the central nervous system (CNS) 3.
Mechanism of Action
- Baclofen acts by activating GABA(B) receptors, which are expressed in various immune cells and the central nervous system 3, 4.
- The activation of these receptors leads to presynaptic inhibition, reducing spastic tone at the spinal cord level when administered intrathecally 4.
- Baclofen's action on GABA(B) receptors also desensitizes chemokine receptors and suppresses inflammation, contributing to its anti-spasticity and potential anti-inflammatory effects 3.
Therapeutic Applications
- Baclofen is used clinically to treat severe spasticity unresponsive to oral antispasmodics, with its effectiveness enhanced when delivered intrathecally to act directly on the spinal cord 5, 4.
- It has shown potential in alleviating collagen-induced arthritis and regulating dendritic cells, suggesting a role in treating autoimmune diseases 3.
- Baclofen also exhibits antinociceptive effects, particularly in models of peripheral neuropathy, although its effectiveness in neuropathic pain is still under investigation 6.