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A summary of mechanistic hypotheses of gabapentin pharmacology.
- Source :
-
Epilepsy research [Epilepsy Res] 1998 Feb; Vol. 29 (3), pp. 233-49. - Publication Year :
- 1998
-
Abstract
- Although the cellular mechanisms of pharmacological actions of gabapentin (Neurontin) remain incompletely described, several hypotheses have been proposed. It is possible that different mechanisms account for anticonvulsant, antinociceptive, anxiolytic and neuroprotective activity in animal models. Gabapentin is an amino acid, with a mechanism that differs from those of other anticonvulsant drugs such as phenytoin, carbamazepine or valproate. Radiotracer studies with [14C]gabapentin suggest that gabapentin is rapidly accessible to brain cell cytosol. Several hypotheses of cellular mechanisms have been proposed to explain the pharmacology of gabapentin: 1. Gabapentin crosses several membrane barriers in the body via a specific amino acid transporter (system L) and competes with leucine, isoleucine, valine and phenylalanine for transport. 2. Gabapentin increases the concentration and probably the rate of synthesis of GABA in brain, which may enhance non-vesicular GABA release during seizures. 3. Gabapentin binds with high affinity to a novel binding site in brain tissues that is associated with an auxiliary subunit of voltage-sensitive Ca2+ channels. Recent electrophysiology results suggest that gabapentin may modulate certain types of Ca2+ current. 4. Gabapentin reduces the release of several monoamine neurotransmitters. 5. Electrophysiology suggests that gabapentin inhibits voltage-activated Na+ channels, but other results contradict these findings. 6. Gabapentin increases serotonin concentrations in human whole blood, which may be relevant to neurobehavioral actions. 7. Gabapentin prevents neuronal death in several models including those designed to mimic amyotrophic lateral sclerosis (ALS). This may occur by inhibition of glutamate synthesis by branched-chain amino acid aminotransferase (BCAA-t).
- Subjects :
- Acetates pharmacokinetics
Analgesics pharmacology
Analgesics therapeutic use
Animals
Anti-Anxiety Agents administration & dosage
Anti-Anxiety Agents therapeutic use
Anticonvulsants pharmacology
Anticonvulsants therapeutic use
Brain drug effects
Brain physiology
Calcium Channels chemistry
Calcium Channels drug effects
Calcium Channels physiology
Gabapentin
Humans
Models, Neurological
Neuroprotective Agents pharmacology
Neuroprotective Agents therapeutic use
Neurotransmitter Agents physiology
Pain
Sodium Channels physiology
Synapses drug effects
Synapses physiology
Tissue Distribution
Acetates pharmacology
Acetates therapeutic use
Amines
Cyclohexanecarboxylic Acids
gamma-Aminobutyric Acid metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0920-1211
- Volume :
- 29
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Epilepsy research
- Publication Type :
- Academic Journal
- Accession number :
- 9551785
- Full Text :
- https://doi.org/10.1016/s0920-1211(97)00084-3