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| Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication primarily used to treat neuropathic pain and also for partial seizures of epilepsy. It is a commonly used medication for the treatment of neuropathic pain caused by diabetic neuropathy, postherpetic neuralgia, and central pain. It is moderately effective: about 30–40% of those given gabapentin for diabetic neuropathy or postherpetic neuralgia have a meaningful benefit.
Gabapentin, like other gabapentinoid drugs, acts by decreasing activity of the α2δ-1 protein, coded by the CACNA2D1 gene, first known as an auxiliary subunit of voltage gated calcium channels. However, see Pharmacodynamics, below. By binding to α2δ-1, gabapentin reduces the release of excitatory neurotransmitters (primarily glutamate) and as a result, reduces excess excitation of neuronal networks in the spinal cord and brain. Sleepiness and dizziness are the most common side effects. Serious side effects include respiratory depression, and allergic reactions. As with all other antiepileptic drugs approved by the FDA, gabapentin is labeled for an increased risk of suicide. Lower doses are recommended in those with kidney disease.
Gabapentin was first approved for use in the United Kingdom in 1993. It has been available as a generic medication in the United States since 2004. It is the first of several other drugs that are similar in structure and mechanism, called gabapentinoids. In 2022, it was the tenth most commonly prescribed medication in the United States, with more than 40 million prescriptions. During the 1990s, Parke-Davis, a subsidiary of Pfizer, used a number of illegal techniques to encourage physicians in the United States to prescribe gabapentin for unapproved uses. They have paid out millions of dollars to settle lawsuits regarding these activities.
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Read full article at Wikipedia
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| InChI=1S/C9H17NO2/c10-7-9(6-8(11)12)4-2-1-3-5-9/h1-7,10H2,(H,11,12) |
| UGJMXCAKCUNAIE-UHFFFAOYSA-N |
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environmental contaminant
Any minor or unwanted substance introduced into the environment that can have undesired effects.
Bronsted base
A molecular entity capable of accepting a hydron from a donor (Bronsted acid).
(via organic amino compound )
Bronsted acid
A molecular entity capable of donating a hydron to an acceptor (Bronsted base).
(via oxoacid )
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calcium channel blocker
One of a class of drugs that acts by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools.
xenobiotic
A xenobiotic (Greek, xenos "foreign"; bios "life") is a compound that is foreign to a living organism. Principal xenobiotics include: drugs, carcinogens and various compounds that have been introduced into the environment by artificial means.
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anticonvulsant
A drug used to prevent seizures or reduce their severity.
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View more via ChEBI Ontology
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[1-(aminomethyl)cyclohexyl]acetic acid
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gabapentin
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KEGG DRUG
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gabapentina
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WHO MedNet
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gabapentine
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DrugBank
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gabapentinum
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DrugBank
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1-(Aminomethyl)cyclohexaneacetic acid
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ChemIDplus
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2359739
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Reaxys Registry Number
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Reaxys
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60142-96-3
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CAS Registry Number
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ChemIDplus
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60142-96-3
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CAS Registry Number
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KEGG DRUG
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Bockbrader HN, Budhwani MN, Wesche DL (2013)
Gabapentin to pregabalin therapy transition: a pharmacokinetic simulation.
American journal of therapeutics 20, 32-36 [PubMed:23018586]
[show Abstract]
The objective of this modeling study was to assess different dosage regimens that might be used to guide clinicians in transitioning patients from gabapentin to pregabalin therapy when such a transition is clinically warranted. Two different gabapentin to pregabalin transition designs were simulated based on their respective population pharmacokinetic profiles. The first design involved immediate discontinuation of gabapentin therapy with initiation of pregabalin therapy at the next scheduled dose period. The second design featured a gradual transition involving coadministration of 50% of the gabapentin dosage and 50% of the desired pregabalin dosage for 4 days, followed by discontinuation of gabapentin and fully targeted dosages of pregabalin. Both transition designs were studied at 3 dosage levels: gabapentin 900 mg/d to pregabalin 150 mg/d, gabapentin 1800 mg/d to pregabalin 300 mg/d, and gabapentin 3600 mg/d to pregabalin 600 mg/d. Overall drug exposure achieved during the 2 transition designs was the sum of the gabapentin and pregabalin concentrations, expressed as pregabalin-equivalent concentrations. The pharmacokinetic simulations show that during the transition period in both designs, predicted pregabalin-equivalent concentrations did not depart from those calculated during periods of steady-state gabapentin or pregabalin monotherapy. Transition from gabapentin to pregabalin was seamless and rapid, with predicted pregabalin-equivalent concentrations highly comparable with plasma pregabalin concentrations within 1 day of pregabalin initiation in the immediate discontinuation model and within 1 day of gabapentin cessation in the gradual discontinuation model. These data suggest that transitioning patients from gabapentin to pregabalin could theoretically be achieved by either of the 2 approaches assessed. | Chen C, Cowles VE, Sweeney M (2013)
The intestinal absorption mechanism of gabapentin makes it appropriate for gastroretentive delivery.
Current clinical pharmacology 8, 67-72 [PubMed:22946876]
[show Abstract]
Gabapentin is approved for the treatment of postherpetic neuralgia (PHN) and epilepsy. The pharmacokinetic (PK) properties of gabapentin, including absorption, distribution, metabolism, and excretion (ADME), were investigated during the development of Neurontin®, an immediate-release (IR) formulation of gabapentin that is orally administered three-times daily. Recently, a gastroretentive (GR) once-daily formulation of gabapentin (Gralise®) has been developed and marketed for the treatment of PHN. This review focuses on the ADME properties of gabapentin and illustrates how GR delivery enhances its absorption compared with IR formulations and allows once-daily dosing with the evening meal for the treatment of PHN. It includes the following aspects: 1) the mechanism of gastroretention of gabapentin GR tablets, 2) in vitro dissolution profiles of the GR and IR formulations, 3) site of absorption of gabapentin in the human intestine, 4) studies of the mechanism of gabapentin absorption using intestinal tissue preparations, 5) human PK studies to examine the effects of dose and formulations on PK profiles and the bioavailability of gabapentin at therapeutically relevant doses, and 6) efficacy and safety of gastroretentive gabapentin in patients with PHN. The data reviewed support that GR delivery of gabapentin optimizes its absorption via a saturable uptake mechanism. The prolonged residence of the GR tablets in the stomach coupled with the gradual release of gabapentin attenuates saturation of the transporter, thus enhancing absorption and increasing bioavailability, especially at therapeutically relevant doses. The net result is a once-daily formulation of gabapentin that is well tolerated and efficacious for the treatment of PHN. | Anand S (2013)
Gabapentin for pruritus in palliative care.
The American journal of hospice & palliative care 30, 192-196 [PubMed:22556282]
[show Abstract]
Itch/pruritus can be very distressing in palliative care population and often is difficult to treat. Conventional antihistamines lack efficacy. Cutaneous and central pathogenesis of itch is extremely complex and unclear, making its treatment challenging. Neuronal mechanisms have been identified in the pathophysiology of itch hence providing a myriad of therapeutic options. It has been established that pruritus and pain neuronal pathway interact with each other, hence neuropathic analgesics like gabapentin has shown to be efficacious antipruritic therapeutic option. Gabapentin impedes transmitting nociceptive sensations to brain, thus also suppressing pruritus. Gabapentin is safe and found to be effective in uremic pruritus, cancer/hematologic causes, opiod-induced itch, brachioradial pruritis, burns pruritus, and pruritus of unknown origin. Further research is required in this area to establish whether gabapentin is consistently effective. | Aydin ON, Ek RO, Temoçin S, Uğur B, Alaçam B, Şen S (2012)
The antinociceptive effects of systemic administration of tramadol, gabapentin and their combination on mice model of acute pain.
Agri : Agri (Algoloji) Dernegi'nin Yayin organidir = The journal of the Turkish Society of Algology 24, 49-55 [PubMed:22865488]
[show Abstract]
ObjectivesThe aim of the present study was to investigate the possible antinociceptive effects of systemic administration of tramadol and gabapentin either alone or in combination on acute pain models in mice.MethodsAfter obtaining the approval of Animal Ethics Committee; 96 BALB/c albino male mice were divided into 12 groups: (I) control without injection, (II) control treated with saline, (III)-(IV) mice treated with tramadol 10 mg/kg or 30 mg/kg, (V)-(VIII) mice treated with gabapentin; 30, 100, 200, 300 mg/kg respectively. In order to determine possible interactions between tramadol gabapentin and; mice received four different combinations of tramadol + gabapentin (30+30, 30+100, 30+200 and 30+300 mg/kg) (Groups IX-XII respectively). Mice received 0.1 ml solution for every 10 g of their weight. The drug was injected into peritonea. Thirty minutes after the drug injection, tail-flick and hot-plate tests were conducted.ResultsTen and 30 mg/kg tramadol produced dose dependent antinociceptive effect in tail-flick and hot plate tests. Gabapentin had no antinociceptive effect in the tail flick test except 300 mg/kg dose, and had dose dependent antinociceptive effect in hot-plate test. In both tests, various combinations of tramadol and gabapentin produced an antinociceptive effect that is greater than that produced by tramadol and gabapentin alone. But, just 30 mg/kg tramadol + 300 mg/kg gabapentin combination caused statistically significant increase in both tests (p<0.05).ConclusionWhen gabapentin and tramadol were used in combination, gabapentin had no additive antinociceptive effect except for 300 mg/kg in tail-flick and hot-plate tests. Tail-flick test showed that tramadol produced better antinociceptive effect than gabapentin. | Narai Y, Imamachi N, Saito Y (2012)
Gabapentin augments the antihyperalgesic effects of diclofenac sodium through spinal action in a rat postoperative pain model.
Anesthesia and analgesia 115, 189-193 [PubMed:22467888]
[show Abstract]
BackgroundGabapentin and nonsteroidal antiinflammatory drugs (NSAIDs) attenuate postoperative pain and neuropathic pain in humans. The combination of gabapentin and NSAIDs is effective for postoperative pain and enhances functional recovery after surgery. Intrathecal administration of gabapentin or NSAIDs inhibits hyperalgesia in a rat postoperative pain model. However, there is no information on the effects of intrathecal administration of a combination of gabapentin and NSAIDs. We therefore investigated the effects of intrathecal administration of gabapentin and NSAIDs in a rat model of postoperative pain.MethodsRats were prepared for intrathecal catheters under halothane anesthesia. Two days after catheterization, gabapentin (4, 40, or 400 μg per 20 μL of saline), diclofenac sodium, a nonselective cyclooxygenase inhibitor (2, 20, or 200 μg per 20 μL of 6% glucose), 20 μL saline, 20 μL 6% glucose, and a combination of gabapentin and diclofenac (40 μg gabapentin + 20 μg diclofenac and 4 μg gabapentin + 2 μg diclofenac per 20 μL 6% glucose) were injected intrathecally. We performed a hindpaw incision 30 minutes after injection. Each group consisted of 6 rats. The mechanical threshold was measured to evaluate secondary hyperalgesia using von Frey filaments before intrathecal catheterization and at 2 hours, and 1, 3, 5, and 7 days after paw incision.ResultsGabapentin 400 μg attenuated mechanical hyperalgesia for 7 days compared with the control group. Diclofenac 200 μg inhibited hyperalgesia for 5 days compared with the control group. The 40 μg gabapentin + 20 μg diclofenac group had a significantly reduced secondary hyperalgesic response in 2 hours and 1 day compared with 40 μg gabapentin and 20 μg diclofenac, respectively. The 4 μg gabapentin + 2 μg diclofenac group had a significantly reduced secondary hyperalgesic response in 2 hours and 1 day compared with 2 μg diclofenac. The withdrawal threshold on the contralateral paw did not change compared with the preincision threshold.ConclusionIntrathecal administration of gabapentin and diclofenac in combination reduced secondary hyperalgesia at doses having no antihyperalgesic effects when given individually. Our results suggest that gabapentin and diclofenac have an important role in postoperative pain reduction at the spinal level, and that gabapentin augments the antihyperalgesic effects of diclofenac through action in the spinal cord. | Lavigne JE, Heckler C, Mathews JL, Palesh O, Kirshner JJ, Lord R, Jacobs A, Amos E, Morrow GR, Mustian K (2012)
A randomized, controlled, double-blinded clinical trial of gabapentin 300 versus 900 mg versus placebo for anxiety symptoms in breast cancer survivors.
Breast cancer research and treatment 136, 479-486 [PubMed:23053645]
[show Abstract]
Gabapentin is used for the treatment of hot flashes and neuropathic pain in breast cancer survivors, and is commonly used off-label for the treatment of anxiety. Yet, clinical trial evidence to support the use of gabapentin for anxiety symptoms is lacking. In a randomized, double-blinded controlled trial we compared 300 mg gabapentin versus 900 mg gabapentin versus placebo. Subjects were 420 breast cancer patients who had completed all chemotherapy cycles. Anxiety traits and current (state) anxiety were measured using the Speilberger Strait-Trait Anxiety Inventory at baseline, 4 and 8 weeks. Pain was measured at baseline using a 10-point scale. Analyses included analysis of covariance and ordinary least squares regression. At 4 weeks, state anxiety change scores were significantly better for gabapentin 300 and 900 mg (p = 0.005) compared to placebo. The magnitude of improvement was proportional to baseline state anxiety. At 8 weeks, the anxiolytic effects of gabapentin compared to placebo persisted (p < 0.005). We found no significant interactions. The lower dose (300 mg) was associated with the best treatment outcomes for all patients except those with the highest baseline anxiety. Given its similar pharmacology, efficacy in the treatment of hot flashes, and low cost, gabapentin may provide a low cost and parsimonious alternative treatment choice for breast cancer survivors presenting in primary care practices with anxiety symptoms. Gabapentin is effective for hot flashes, and, therefore, may provide therapeutic benefit for both anxiety and hot flashes at a generic drug price. For patients reluctant to take a controlled substance, such as a benzodiazepine, gabapentin may offer an alternative therapy. Similarly, patients with a history of substance use may benefit from gabapentin without risk of addiction or abuse. For cancer survivors experiencing both hot flashes and anxiety, gabapentin may provide a single effective treatment for both and is an alternative therapy for anxiety for patients unwilling to take a benzodiazepine or those with a history of substance use. | Hosseini-Zare MS, Dashti-Khavidaki S, Mahdavi-Mazdeh M, Ahmadi F, Akrami S (2012)
Peripheral neuropathy response to erythropoietin in type 2 diabetic patients with mild to moderate renal failure.
Clinical neurology and neurosurgery 114, 663-667 [PubMed:22296650]
[show Abstract]
This study assessed the added effect of 6 months of erythropoietin (EPO) administration in patients suffering from diabetic neuropathy with mild to moderate chronic kidney disease (CKD) managed with gabapentin. Twenty diabetic patients with mild to moderate CKD were included; 12 in gabapentin and 8 in EPO+gabapentin group. The subjects underwent nerve conduction studies (NCS) at the initiation of the investigation and after 6-month treatment. NCS were made in deep and superficial peroneal, tibial, and sural nerves. After 6 months, in both the groups, proximal motor latency (PML) nonsignificantly improved in deep peroneal and tibial nerves; conversely, dorsal motor latency (DML) got slightly impaired in these two nerves. A nonsignificant disruption and improvement was observed in deep peroneal and tibial motor nerve conduction velocity (MNCV), respectively, in gabapentin group. Although the F-wave of tibial and deep peroneal nerves remained stable in gabapentin group, a nonsignificant improvement was observed in EPO+gabapentin group. H-reflex of tibial nerve and all the evaluated parameters of sural and superficial peroneal nerves remained constant in all patients. Thus, it can be concluded that 6-month administration of EPO+gabapentin, or gabapentin alone in mild to moderate CKD patients with diabetic neuropathy could not improve nerve performance. | Guglielmo R, Martinotti G, Janiri L (2012)
Gabapentin as add-on treatment for somatoform disorder: a case report.
Clinical neuropharmacology 35, 45-46 [PubMed:22240859]
[show Abstract]
Somatoform disorder is a relatively common and severe disorder for which pharmacotherapy has been minimally studied. We report a case of 30-year-old woman with treatment-resistant somatoform disorder that was successfully treated with add-on treatment of gabapentin. Our result showed that gabapentin 1800 mg/day could be tried in case of treatment-resistant somatoform disorder as an add-on strategy. However, controlled trials are needed to investigate the effectiveness of gabapentin in the management of this condition. | Dalkara S, Karakurt A (2012)
Recent progress in anticonvulsant drug research: strategies for anticonvulsant drug development and applications of antiepileptic drugs for non-epileptic central nervous system disorders.
Current topics in medicinal chemistry 12, 1033-1071 [PubMed:22352861]
[show Abstract]
Major advances in antiepileptic drug therapy have taken place since 1950s. In the first period, several antiepileptic drugs (AEDs) such as phenobarbital, diphenylhydantoin, ethosuximide, carbamazepine, benzodiazepines and valproic acid were introduced to epilepsy treatment. After 1990 many new generation drugs (lamotrigine, topiramate, gabapentine, pregabaline, felbamate, lacosamide, levetiracetam etc.) have been developed. These novel AEDs have offered some advantages such as fewer side effects, fewer drug-drug interactions, and better pharmacokinetic properties. But pharmacoresistance and therapeutic failure in 20-25% of the patients remain the main reasons to continue efforts to find safer and more efficacious drugs and ultimate a treatment for this devastating disease. Several AEDs especially novel compounds have been found to be effective also in the treatment of several other neurologic and psychiatric disorders. Chemical diversity of the newer antiepileptic drugs as well as those currently in clinical development is another point that encourages medicinal chemists to study this subject. This review summarizes recent studies on the development of potential anticonvulsant compounds in different chemical structures, their structure-activity relationships and also therapeutic usages of AEDs other than epilepsy. | Yagi T, Naito T, Mino Y, Umemura K, Kawakami J (2012)
Impact of concomitant antacid administration on gabapentin plasma exposure and oral bioavailability in healthy adult subjects.
Drug metabolism and pharmacokinetics 27, 248-254 [PubMed:22240839]
[show Abstract]
The aim of this open-label, randomized, and 3-period crossover study was to evaluate the influences of concomitant antacid administration on the plasma disposition, intestinal absorption, and urinary excretion of gabapentin in humans. Gabapentin (200 mg) was orally administered alone, with 1 g magnesium oxide (MgO), or with 20 mg omeprazole to 13 healthy adult subjects. Oral bioavailability (BA) of gabapentin was estimated by 24-h urine collection. The C(max), T(max) and AUC(0-∞) of gabapentin + MgO were significantly lower than that of gabapentin alone (by 33%, 36% and 43%, respectively) and gabapentin + omeprazole (by 29%, 46% and 40%, respectively). In contrast, no significant differences were observed in the plasma disposition parameters of gabapentin between the treatments with and without omeprazole. The gabapentin BA in the MgO treatment was significantly lower, by 32% and 39%, compared to the gabapentin alone and with omeprazole treatment, respectively. There was no significant difference in the gabapentin BA between the gabapentin alone and with omeprazole treatment. Concomitant MgO and omeprazole did not affect the renal clearance of gabapentin. In conclusion, concomitant MgO decreased the gabapentin exposure through the reduction of intestinal absorption extent and rate. This reduction may be independent of the suppression of gastrointestinal acidification caused by antacids. | Neelakantan H, Walker EA (2012)
Temperature-dependent enhancement of the antinociceptive effects of opioids in combination with gabapentin in mice.
European journal of pharmacology 686, 55-59 [PubMed:22575516]
[show Abstract]
Prescription opioids and anticonvulsants such as gabapentin are often used as combination therapeutics for chronic as well as acute post-operative pain conditions although the effectiveness of such combinations may be dependent on the intensity of the pain state. To test the capacity of gabapentin to enhance opioid effectiveness in the presence of different thermal stimulus intensities, morphine, oxycodone and gabapentin were examined alone and in combination for antinociception in Swiss-Webster male mice using a hot-plate set to one of three temperature intensities (48.5°C, 50.5°C, 52.5°C). Morphine and oxycodone produced significant dose- and stimulus intensity-dependent antinociception whereas gabapentin produced only modest antinociception. However, in combination, gabapentin enhanced the effectiveness of sub-antinociceptive doses of morphine and oxycodone and the gabapentin and oxycodone combinations were both dose- and temperature intensity-dependent. These results provide evidence that the effectiveness and magnitude of the interactions between gabapentin and opioids are dependent on the intensity of the pain stimulus in acute thermal pain states. | Chen Z, Janes K, Chen C, Doyle T, Bryant L, Tosh DK, Jacobson KA, Salvemini D (2012)
Controlling murine and rat chronic pain through A3 adenosine receptor activation.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology 26, 1855-1865 [PubMed:22345405]
[show Abstract]
Clinical management of chronic neuropathic pain is limited by marginal effectiveness and unacceptable side effects of current drugs. We demonstrate A(3) adenosine receptor (A(3)AR) agonism as a new target-based therapeutic strategy. The development of mechanoallodynia in a well-characterized mouse model of neuropathic pain following chronic constriction injury of the sciatic nerve was rapidly and dose-dependently reversed by the A(3)AR agonists: IB-MECA, its 2-chlorinated analog (Cl-IB-MECA), and the structurally distinct MRS1898. These effects were naloxone insensitive and thus are not opioid receptor mediated. IB-MECA was ≥1.6-fold more efficacious than morphine and >5-fold more potent. In addition, IB-MECA was equally efficacious as gabapentin (Neurontin) or amitriptyline, but respectively >350- and >75-fold more potent. Besides its potent standalone ability to reverse established mechanoallodynia, IB-MECA significantly increased the antiallodynic effects of all 3 analgesics. Moreover, neuropathic pain development in rats caused by widely used chemotherapeutics in the taxane (paclitaxel), platinum-complex (oxaliplatin), and proteasome-inhibitor (bortezomib) classes was blocked by IB-MECA without antagonizing their antitumor effect. A(3)AR agonist effects were blocked with A(3)AR antagonist MRS1523, but not with A(1)AR (DPCPX) or A(2A)AR (SCH-442416) antagonists. Our findings provide the scientific rationale and pharmacological basis for therapeutic development of A(3)AR agonists for chronic pain. | Rabchevsky AG, Patel SP, Lyttle TS, Eldahan KC, O'Dell CR, Zhang Y, Popovich PG, Kitzman PH, Donohue KD (2012)
Effects of gabapentin on muscle spasticity and both induced as well as spontaneous autonomic dysreflexia after complete spinal cord injury.
Frontiers in physiology 3, 329 [PubMed:22934077]
[show Abstract]
We recently reported that the neuropathic pain medication, gabapentin (GBP; Neurontin), significantly attenuated both noxious colorectal distension (CRD)-induced autonomic dysreflexia (AD) and tail pinch-induced spasticity compared to saline-treated cohorts 2-3 weeks after complete high thoracic (T4) spinal cord injury (SCI). Here we employed long-term blood pressure telemetry to test, firstly, the efficacy of daily versus acute GBP treatment in modulating AD and tail spasticity in response to noxious stimuli at 2 and 3 weeks post-injury. Secondly, we determined whether daily GBP alters baseline cardiovascular parameters, as well as spontaneous AD events detected using a novel algorithm based on blood pressure telemetry data. At both 14 and 21 days after SCI, irrespective of daily treatment, acute GBP given 1 h prior to stimulus significantly attenuated CRD-induced AD and pinch-evoked tail spasticity; conversely, acute saline had no such effects. Moreover, daily GBP did not alter 24 h mean arterial pressure (MAP) or heart rate (HR) values compared to saline treatment, nor did it reduce the incidence of spontaneous AD events compared to saline over the three week assessment period. Power spectral density (PSD) analysis of the MAP signals demonstrated relative power losses in mid frequency ranges (0.2-0.8 Hz) for all injured animals relative to low frequency MAP power (0.02-0.08 Hz). However, there was no significant difference between groups over time post-injury; hence, GBP had no effect on the persistent loss of MAP fluctuations in the mid frequency range after injury. In summary, the mechanism(s) by which acute GBP treatment mitigate aberrant somatosensory and cardiophysiological responses to noxious stimuli after SCI remain unclear. Nevertheless, with further refinements in defining the dynamics associated with AD events, such as eliminating requisite concomitant bradycardia, the objective repeatability of automatic detection of hypertensive crises provides a potentially useful tool for assessing autonomic function pre- and post-SCI, in conjunction with experimental pharmacotherapeutics for neuropathic pain, such as GBP. | Boutet G (2012)
[Management of hot flushes for breast cancer survivors].
Gynecologie, obstetrique & fertilite 40, 241-254 [PubMed:22464746]
[show Abstract]
Hot flushes experienced by breast cancer survivors present specific issues due to their frequency, severity and difficulty to treat. After an evaluation of her symptoms and expression of her expectations and requests, each patient will be provided a clear, synthetic, comprehensible, supported and prioritized view of all treatment options. Any prescribed treatment will be a shared medical decision making. An algorithm of treatment propositions, documented by evidence-based medicine, is proposed. As randomized trials show that placebo-induced reduction of hot flushes frequency represents to 25 to 75%, non-pharmacological approaches selected by the patient should be preferred at first, to the exception however of phytoestrogens. The first-line treatment for severe hot flushes should be, depending on each specific context, venlafaxine, paroxetine or gabapentine. In case of inefficiency, treatments of second- and third-line will be proposed. Prescription of progestin or of a menopausal hormone therapy should remain exceptional and limited to cases where all other treatments failed, after obtaining the patient's informed consent following exhaustive information. Indications of stellate ganglion block remain to be defined. | Guddati AK, Zafar Z, Cheng JT, Mohan S (2012)
Treatment of gabapentin-induced myoclonus with continuous renal replacement therapy.
Indian journal of nephrology 22, 59-61 [PubMed:22279347]
[show Abstract]
A 56-year-old man with diabetes, hypertension, and chronic kidney disease presented to the emergency room with a complaint of pain in his right foot. He was found to have tremors. Gabapentin toxicity was suspected and the patient was found to have high gabapentin level (6.3 mcg/ml). Patient was commenced on continuous venovenous hemodiafiltration (CVVHD) and the pharmacokinetics of gabapentin was studied. The patient improved symptomatically and his tremors subsided. In this case report, we describe the successful management of gabapentin toxicity with continuous renal replacement therapy and calculate the clearance of gabapentin which will enable future treatment of gabapentin toxicity by CVVHD. | Wei X, Wei W (2012)
Role of gabapentin in preventing fentanyl- and morphine-withdrawal-induced hyperalgesia in rats.
Journal of anesthesia 26, 236-241 [PubMed:22048285]
[show Abstract]
PurposeThis study was undertaken to examine the effect of gabapentin for preventing hyperalgesia induced by morphine and fentanyl withdrawal in rats.MethodsTo induce hyperalgesia, Sprague Dawley (SD) rats were subcutaneously injected with fentanyl four times at 15-min intervals (60 μg/kg per injection), resulting in total dose of 240 μg/kg over 1 h, and morphine 10 mg/kg twice daily for 7 days. The effect of gabapentin was detected with behavioral tail-flick and paw-withdrawal tests.ResultsDrug termination produced significant decrease in antinociception thresholds (P < 0.05 vs. saline group), indicating that the rats became sensitive to thermal stimuli. In rats that received combined treatment with fentanyl/morphine and gabapentin (25/50 mg/kg), results demonstrated that there were no significant decreases in antinociception thresholds (vs. saline group) after opioid withdrawal. Gabapentin (50 mg/kg) could also prevent morphine tolerance. The 50% effective dose (ED50) value was 12.5 mg/kg in tail-flick and 13.6 mg/kg in paw-withdrawal tests.ConclusionsThe study showed that gabapentin can significantly prevented opioid-induced hyperalgesia (OIH) induced caused by fentanyl and morphine, suggesting a role for the addition of gabapentin in the perioperative period and during chronic pain treatment as an effective drug to prevent OIH. | Zong Z, Qiu J, Tinmanee R, Kirsch LE (2012)
Kinetic model for solid-state degradation of gabapentin.
Journal of pharmaceutical sciences 101, 2123-2133 [PubMed:22419014]
[show Abstract]
Gabapentin degrades directly to gabapentin-lactam (gaba-L) in the solid state. The objective of this study was to formulate a drug degradation model that accounted for the environmental storage conditions and mechanical stress (prior to storage) on lactamization kinetics. The effects of mechanical stress on drug degradation kinetics were determined by milling gabapentin in a FRITSCH Planetary Micro Mill for 0 and 60 min. The resultant gabapentin powder was stored at 40 °C-60 °C and 5%-30% relative humidity. The rate of gaba-L formation was measured by high-performance liquid chromatography. An irreversible two-step autocatalytic reaction scheme was fit using nonlinear regression methods. The resultant kinetic model was used to predict the time-dependent concentration of degradant of gabapentin tablets prepared under various exemplary manufacturing conditions, thereby demonstrating the ability of the model to link manufacturing variation and chemical stability in solid-state gabapentin formulations. | Wittayalertpanya S, Chompootaweep S, Thaworn N, Khemsri W, Prompila N, Sayankuldilok N, Punyasang W (2012)
Pharmacokinetic of gabapentin 600 mg tablet in Thai healthy subjects.
Journal of the Medical Association of Thailand = Chotmaihet thangphaet 95, 583-589 [PubMed:22612015]
[show Abstract]
BackgroundGabapentin is an antiepileptic drug. It is structurally similar to yaminobutyric acid (GABA), which crosses the blood-brain barrier. Gabapentin is absorbed into the blood by the L-amino acid transport system. The oral bioavailability of gabapentin displays dose-dependence. Plasma concentrations ofgabapentin are not directly proportional to dose. Therefore, pharmacokinetic of gabapentin is essential for patients who have to receive gabapentin 600 mg.ObjectiveTo investigate the pharmacokinetic of gabapentin 600 mg in Thai healthy subjects.Material and methodThe present study was performed on 24 healthy Thai male subjects who received a single oral dose of 600 mg gabapentin tablet. Serial blood samples were collected before and to 48 hours after drug administration. Plasma gabapentin concentrations were determined by automated High Performance Liquid Chromatography (HPLC) with UV detector after deproteinized with acetonitrile followed by derivatization with 1-fluoro-2,4-dinitrobenzene. The relevant pharmacokinetic parameters were determined.ResultsThe mean values of pharmacokinetic parameters (mean +/- SD) were 3.17 +/- 0.80 hour (1.5 to 5.0 hour) for T; 4,853.58 +/- 1,369.67 ng/ml for Cm; 0.11 +/- 0.02 hour for Kel, 6.62 +/- 1.87 hour (4.89 to 11.41 hour) for T1/2; 47,712.88 +/- 12,853.61 ng.hour/ml for AUC0-t, 48,713.20 +/- 12,909.78 ng.hour/ml for AUC0-inf, 5.24 +/- 1.32 L/hour for CI, and 49.28 +/- 15.98 L for Vd.ConclusionThe data show the pharmacokinetic parameters of gabapentin 600 mg. These data should be used to support the assignment of therapeutic purposes for patients who have to receive gabapentin 600 mg. | Irizarry MC, Webb DJ, Boudiaf N, Logie J, Habel LA, Udaltsova N, Friedman GD (2012)
Risk of cancer in patients exposed to gabapentin in two electronic medical record systems.
Pharmacoepidemiology and drug safety 21, 214-225 [PubMed:22144034]
[show Abstract]
PurposeHigh doses of gabapentin were associated with pancreatic acinar cell tumors in male Wistar rats, but there is little published epidemiological data regarding gabapentin and carcinogenicity. We explored the association between gabapentin and cancer in a US medical care program and followed up nominally significant associations in a UK primary care database.MethodsIn the US Kaiser Permanente Northern California (KPNC) health system, we performed nested case-control analyses of gabapentin and 55 cancer sites and all cancers combined using conditional logistic regression. Up to 10 controls were matched to each case on year of birth, sex, and year of cohort entry. No other covariates were included in models. Only dispensings for gabapentin 2 years or more before index date were considered. Nominally significant associations with an OR > 1.00 and p < 0.05 for three or more dispensings versus no dispensings were followed up by similar nested case-control analyses in the UK General Practice Research Database (GPRD), adjusting for potential indications for gabapentin and risk factors for the specific cancers.ResultsThe following analyses had OR > 1.00 and p < 0.05 for three or more dispensings of gabapentin versus no dispensing (2-year lag) in KPNC and were also examined in the GPRD: all cancers, breast, lung and bronchus, urinary bladder, kidney/renal pelvis, stomach, anus/anal canal/anorectum, penis, and other nervous system. These cancers were not statistically significantly associated with gabapentin in the GPRD case-control studies (2-year lag). The GPRD and KPNC studies did not identify a statistically significant increased risk of pancreatic cancer with more than two prescriptions of gabapentin in the 2-year lagged analyses.ConclusionsThe epidemiological data in a US cohort with up to 12 years of follow-up and a UK cohort with up to 15 years of follow-up do not support a carcinogenic effect of gabapentin use. However, the confidence intervals for some analyses were wide, and an important effect cannot be confidently excluded. | Vedula SS, Goldman PS, Rona IJ, Greene TM, Dickersin K (2012)
Implementation of a publication strategy in the context of reporting biases. A case study based on new documents from Neurontin litigation.
Trials 13, 136 [PubMed:22888801]
[show Abstract]
BackgroundPrevious studies have documented strategies to promote off-label use of drugs using journal publications and other means. Few studies have presented internal company communications that discussed financial reasons for manipulating the scholarly record related to off-label indications. The objective of this study was to build on previous studies to illustrate implementation of a publication strategy by the drug manufacturer for four off-label uses of gabapentin (Neurontin, Pfizer, Inc.): migraine prophylaxis, treatment of bipolar disorders, neuropathic pain, and nociceptive pain.MethodsWe included in this study internal company documents, email correspondence, memoranda, study protocols and reports that were made publicly available in 2008 as part of litigation brought by consumers and health insurers against Pfizer for fraudulent sales practices in its marketing of gabapentin (see http://pacer.mad.uscourts.gov/dc/cgi-bin/recentops.pl?filename=saris/pdf/ucl%20opinion.pdf for the Court's findings).We reviewed documents pertaining to 20 clinical trials, 12 of which were published. We categorized our observations related to reporting biases and linked them with topics covered in internal documents, that is, deciding what should and should not be published and how to spin the study findings (re-framing study results to explain away unfavorable findings or to emphasize favorable findings); and where and when findings should be published and by whom.ResultsWe present extracts from internal company marketing assessments recommending that Pfizer and Parke-Davis (Pfizer acquired Parke-Davis in 2000) adopt a publication strategy to conduct trials and disseminate trial findings for unapproved uses rather than an indication strategy to obtain regulatory approval. We show internal company email correspondence and documents revealing how publication content was influenced and spin was applied; how the company selected where trial findings would be presented or published; how publication of study results was delayed; and the role of ghost authorship.ConclusionsTaken together, the extracts we present from internal company documents illustrate implementation of a strategy at odds with unbiased study conduct and dissemination. Our findings suggest that Pfizer and Parke-Davis's publication strategy had the potential to distort the scientific literature, and thus misinform healthcare decision-makers. |
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