Gabapentin: Difference between revisions

Line 12:

Gabapentin modulates the action of [[glutamate]] decarboxylase (GAD) and branched chain aminotransferase (BCAT), two enzymes involved in [[GABA]] biosynthesis. In human and rat studies, gabapentin was found to increase GABA biosynthesis, and to increase non-synaptic GABA neurotransmission in vitro.<ref>Mechanisms of action of gabapentin (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/9686247</ref> As the GABA system is the most prolific inhibitory receptor set within the brain, its increase in biosynthesis results in the [[sedating]] and [[Anxiety_suppression|anxiolytic]] (or [[Anxiety suppression|calming effects]]) of gabapentin on the nervous system.

Gabapentin, as a gabapentinoid, has also been shown to bind to the α2δ-1 subunit of Voltage-Gated Calcium Channels to act as a VGCC blocker, which contributes to its inhibitory, analgesic, and anxiolytic effects. It is uncertain exactly how this method of action contributes to gabapentin's psychoactive effects.

Gabapentin, as a gabapentinoid, has also been shown to bind to the α2δ-1 subunit of Voltage-Gated Calcium Channels to act as a VGCC blocker, which contributes to its inhibitory, analgesic, and anxiolytic effects.<ref>The mechanisms of action of gabapentin and pregabalin. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/16376147</ref> It is uncertain exactly how this method of action contributes to gabapentin's psychoactive effects.

The bioavailability of gabapentin is relatively low and is inversely proportional to the dose (i.e. higher doses have lower biovailability than lower doses). The bioavailability of gabapentin is approximately 60%, 47%,

34%, 33%, and 27% following 900, 1200, 2400, 3600, and 4800 mg/day.<ref>Neurontin Clinical Pharmacology Biopharmaceutics Review | http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-397.pdf_Neurontin_BioPharmr.pdf</ref> Gabapentin is highly lipophilic, making unsaturated fats such as vegetable oil and olive oil significantly boost the total amount of absorption. This means that eating a high fat meal substantially increases gabapentin's bioavailability, due to the fact that unsaturated fats bind to gabapentin to allow for absorption, and that meals slow down and thus increase gabapentin absorption by decreasing gabapentin transporter saturation.<ref>Gabapentin data sheet | http://reference.medscape.com/drug/neurontin-gralise-gabapentin-343011#showall</ref>

Gabapentin transporter saturation occurs when large enough doses of gabapentin are consumed in a short enough period of time to result in the body being unable to absorb any more gabapentin, causing a significant reduction in bioavailability, which largely accounts for the drop in bioavailability seen with increasing doses.

==Subjective effects==

@@ Line 12: / Line 12: @@
 Gabapentin modulates the action of [[glutamate]] decarboxylase (GAD) and branched chain aminotransferase (BCAT), two enzymes involved in [[GABA]] biosynthesis. In human and rat studies, gabapentin was found to increase GABA biosynthesis, and to increase non-synaptic GABA neurotransmission in vitro.<ref>Mechanisms of action of gabapentin (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/9686247</ref> As the GABA system is the most prolific inhibitory receptor set within the brain, its increase in biosynthesis results in the [[sedating]] and [[Anxiety_suppression|anxiolytic]] (or [[Anxiety suppression|calming effects]]) of gabapentin on the nervous system.
-Gabapentin, as a gabapentinoid, has also been shown to bind to the α2δ-1 subunit of Voltage-Gated Calcium Channels to act as a VGCC blocker, which contributes to its inhibitory, analgesic, and anxiolytic effects. It is uncertain exactly how this method of action contributes to gabapentin's psychoactive effects.
+Gabapentin, as a gabapentinoid, has also been shown to bind to the α2δ-1 subunit of Voltage-Gated Calcium Channels to act as a VGCC blocker, which contributes to its inhibitory, analgesic, and anxiolytic effects.<ref>The mechanisms of action of gabapentin and pregabalin. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/16376147</ref> It is uncertain exactly how this method of action contributes to gabapentin's psychoactive effects.
 The bioavailability of gabapentin is relatively low and is inversely proportional to the dose (i.e. higher doses have lower biovailability than lower doses). The bioavailability of gabapentin is approximately 60%, 47%,
 %, 33%, and 27% following 900, 1200, 2400, 3600, and 4800 mg/day.<ref>Neurontin Clinical Pharmacology Biopharmaceutics Review | http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-397.pdf_Neurontin_BioPharmr.pdf</ref> Gabapentin is highly lipophilic, making unsaturated fats such as vegetable oil and olive oil significantly boost the total amount of absorption. This means that eating a high fat meal substantially increases gabapentin's bioavailability, due to the fact that unsaturated fats bind to gabapentin to allow for absorption, and that meals slow down and thus increase gabapentin absorption by decreasing gabapentin transporter saturation.<ref>Gabapentin data sheet | http://reference.medscape.com/drug/neurontin-gralise-gabapentin-343011#showall</ref>
 Gabapentin transporter saturation occurs when large enough doses of gabapentin are consumed in a short enough period of time to result in the body being unable to absorb any more gabapentin, causing a significant reduction in bioavailability, which largely accounts for the drop in bioavailability seen with increasing doses.
 ==Subjective effects==