Gabapentin: Difference between revisions

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'''Gabapentin''' (also known as '''Neurontin''') is a [[psychoactive class::depressant]] substance of the [[chemical class::gabapentinoid]] class which is used as an [[anticonvulsant]], [[analgesic]] and [[anxiolytic]]. It was originally developed to treat epilepsy and is currently used to relieve neuropathic pain and [[restless leg syndrome]].<ref>Restless legs syndrome: clinical presentation diagnosis and treatment | http://www.sleep-journal.com/article/S1389-9457(15)00647-4/abstract</ref> It is recommended as a first line agent for the treatment of neuropathic pain arising from diabetic neuropathy, post-herpetic neuralgia, and central neuropathic pain.<ref>EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/20402746</ref>

Gabapentin is also an effective tool for treating social anxiety disorder, panic disorder<ref>The role of anticonvulsant drugs in anxiety disorders: a critical review of the evidence (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/17502773</ref><ref>Manual of Clinical Psychopharmacology | https://books.google.co.uk/books?id=D3zz1NCm3qcC&pg=PA345&hl=en</ref> and generalized anxiety disorder.<ref>Successful Psychopharmacology: Evidence-Based Treatment Solutions for Achieving Remission | https://books.google.co.uk/books?id=dnAlO_Veu2QC&pg=PA124&hl=en</ref><ref>https://books.google.co.uk/books?id=82oiYYHGNTQC&pg=PA765&hl=en</ref> It is these effects which provide gabapentin with some recreational potential in a manner that can be accurately compared to a mild [[benzodiazepine]]. However, these recreational effects diminish with repeated usage and are most commonly reported by those ~~who try this compound~~ who do not have a tolerance.

Gabapentin is also an effective tool for treating social anxiety disorder, panic disorder<ref>The role of anticonvulsant drugs in anxiety disorders: a critical review of the evidence (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/17502773</ref><ref>Manual of Clinical Psychopharmacology | https://books.google.co.uk/books?id=D3zz1NCm3qcC&pg=PA345&hl=en</ref> and generalized anxiety disorder.<ref>Successful Psychopharmacology: Evidence-Based Treatment Solutions for Achieving Remission | https://books.google.co.uk/books?id=dnAlO_Veu2QC&pg=PA124&hl=en</ref><ref>https://books.google.co.uk/books?id=82oiYYHGNTQC&pg=PA765&hl=en</ref> It is these effects which provide gabapentin with some recreational potential in a manner that can be accurately compared to a mild [[benzodiazepine]]. However, these recreational effects diminish very quickly with repeated usage and are most commonly reported by those who do not have a tolerance to this compound.

The bioavailability of gabapentin is relatively low and is inversely proportional to the dose. This means that 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> ~~Eating~~ a high fat meal substantially increases gabapentin's bioavailability.<ref>Gabapentin data sheet | http://reference.medscape.com/drug/neurontin-gralise-gabapentin-343011#showall</ref>

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 has minimal hydrophilicity, with saturation values of up to 4490mg/L of pure water<ref>https://pubchem.ncbi.nlm.nih.gov/compound/gabapentin#section=Solubility</ref>. It is instead mostly 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. Due to a lack of available unsaturated gabapentin transporters, this results in an inability of transporters to carry gabapentin, resulting in large amounts of gabapentin passing through the digestive system without being used by one's body.

This effect can easily be significantly lessened by taking lower doses more often instead of higher doses less frequently. As a general rule for most individuals, using any more than 250-300mg of gabapentin every 30-40 minutes will result in wasting a significant portion of the total dose of gabapentin, although this number varies depending on the individual. Alkaline environments inhibit absorption of gabapentin, so lowering the pH of one's stomach using acidic substances such as soda/pop will boost bioavailability as well. It is generally not recommended to take antacids 2 hours before or after taking gabapentin, because although not dangerous, it will severely lower the total absorption of gabapentin.<ref><nowiki>https://www.uofmhealth.org/health-library/d03182a1</nowiki></ref>

==Chemistry==

Gabapentin, or 1-(aminomethyl)cyclohexanacetic acid, is an analogue of the neurotransmitter [[GABA]]. It contains a cyclohexane ring bound to a methylamino chain CH3NH2. At the same location, R1, the cyclohexane ring is also substituted with an acetic acid group. Gabapentin is structurally analagous to GABA. GABA contains an amino group bound to the terminal carbon of a butanoic acid chain. The structure of gabapentin contains the secondary carbon R3 of the butanoic acid chain in GABA incorporated into an attached cyclohexane ring, converting it into a tertiary carbon while still maintaining the chain.

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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 ~~subunits~~ 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. It is uncertain exactly how this method of action contributes to gabapentin's psychoactive effects.

==Subjective effects==

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 '''Gabapentin''' (also known as '''Neurontin''') is a [[psychoactive class::depressant]] substance of the [[chemical class::gabapentinoid]] class which is used as an [[anticonvulsant]], [[analgesic]] and [[anxiolytic]]. It was originally developed to treat epilepsy and is currently used to relieve neuropathic pain and [[restless leg syndrome]].<ref>Restless legs syndrome: clinical presentation diagnosis and treatment | http://www.sleep-journal.com/article/S1389-9457(15)00647-4/abstract</ref> It is recommended as a first line agent for the treatment of neuropathic pain arising from diabetic neuropathy, post-herpetic neuralgia, and central neuropathic pain.<ref>EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/20402746</ref>
-Gabapentin is also an effective tool for treating social anxiety disorder, panic disorder<ref>The role of anticonvulsant drugs in anxiety disorders: a critical review of the evidence (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/17502773</ref><ref>Manual of Clinical Psychopharmacology | https://books.google.co.uk/books?id=D3zz1NCm3qcC&pg=PA345&hl=en</ref> and generalized anxiety disorder.<ref>Successful Psychopharmacology: Evidence-Based Treatment Solutions for Achieving Remission | https://books.google.co.uk/books?id=dnAlO_Veu2QC&pg=PA124&hl=en</ref><ref>https://books.google.co.uk/books?id=82oiYYHGNTQC&pg=PA765&hl=en</ref> It is these effects which provide gabapentin with some recreational potential in a manner that can be accurately compared to a mild [[benzodiazepine]]. However, these recreational effects diminish with repeated usage and are most commonly reported by those who try this compound who do not have a tolerance.
+Gabapentin is also an effective tool for treating social anxiety disorder, panic disorder<ref>The role of anticonvulsant drugs in anxiety disorders: a critical review of the evidence (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/17502773</ref><ref>Manual of Clinical Psychopharmacology | https://books.google.co.uk/books?id=D3zz1NCm3qcC&pg=PA345&hl=en</ref> and generalized anxiety disorder.<ref>Successful Psychopharmacology: Evidence-Based Treatment Solutions for Achieving Remission | https://books.google.co.uk/books?id=dnAlO_Veu2QC&pg=PA124&hl=en</ref><ref>https://books.google.co.uk/books?id=82oiYYHGNTQC&pg=PA765&hl=en</ref> It is these effects which provide gabapentin with some recreational potential in a manner that can be accurately compared to a mild [[benzodiazepine]]. However, these recreational effects diminish very quickly with repeated usage and are most commonly reported by those who do not have a tolerance to this compound.
 The bioavailability of gabapentin is relatively low and is inversely proportional to the dose. This means that 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> Eating a high fat meal substantially increases gabapentin's bioavailability.<ref>Gabapentin data sheet | http://reference.medscape.com/drug/neurontin-gralise-gabapentin-343011#showall</ref>
+%, 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 has minimal hydrophilicity, with saturation values of up to 4490mg/L of pure water<ref>https://pubchem.ncbi.nlm.nih.gov/compound/gabapentin#section=Solubility</ref>. It is instead mostly 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. Due to a lack of available unsaturated gabapentin transporters, this results in an inability of transporters to carry gabapentin, resulting in large amounts of gabapentin passing through the digestive system without being used by one's body.
+This effect can easily be significantly lessened by taking lower doses more often instead of higher doses less frequently. As a general rule for most individuals, using any more than 250-300mg of gabapentin every 30-40 minutes will result in wasting a significant portion of the total dose of gabapentin, although this number varies depending on the individual. Alkaline environments inhibit absorption of gabapentin, so lowering the pH of one's stomach using acidic substances such as soda/pop will boost bioavailability as well. It is generally not recommended to take antacids 2 hours before or after taking gabapentin, because although not dangerous, it will severely lower the total absorption of gabapentin.<ref><nowiki>https://www.uofmhealth.org/health-library/d03182a1</nowiki></ref>
 ==Chemistry==
 Gabapentin, or 1-(aminomethyl)cyclohexanacetic acid, is an analogue of the neurotransmitter [[GABA]]. It contains a cyclohexane ring bound to a methylamino chain CH<sub>3</sub>NH<sub>2</sub>. At the same location, R<sub>1</sub>, the cyclohexane ring is also substituted with an acetic acid group. Gabapentin is structurally analagous to GABA. GABA contains an amino group bound to the terminal carbon of a butanoic acid chain. The structure of gabapentin contains the secondary carbon R<sub>3</sub> of the butanoic acid chain in GABA incorporated into an attached cyclohexane ring, converting it into a tertiary carbon while still maintaining the chain.
@@ Line 14: / Line 18: @@
 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 subunits 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. It is uncertain exactly how this method of action contributes to gabapentin's psychoactive effects.
 ==Subjective effects==