Mechanisms of action of valproate: a commentatory

Johannessen, Cecilie U.

doi:10.1016/s0197-0186(00)00013-9

Cited by 346 publications

(244 citation statements)

References 59 publications

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“…It also indirectly increases GABA concentrations in the brain. 43 In a double-blind cross-over study (n=20), Drewes et al 44 examined the effects of a 3 week treatment course of valoproic acid on chronic central pain in individuals who had sustained a SCI. Overall, they found no significant differences between the control and treatment groups; however, there was a trend towards improvement in the treatment group.…”

mentioning

confidence: 99%

A Systematic Review of Pharmacologic Treatments of Pain After Spinal Cord Injury

Teasell

Mehta

Aubut

et al. 2010

Archives of Physical Medicine and Rehabilitation

150

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Objective-To conduct a systematic review of published research on the pharmacological treatment of pain after spinal cord injury (SCI).Data Sources-Medline, CINAHL, EMBASE and PsycINFO databases were searched for articles published 1980 to June 2009 addressing the treatment of pain post SCI. Randomized controlled trials (RCTs) were assessed for methodological quality using the PEDro assessment scale, while non-RCTs were assessed using the Downs and Black evaluation tool. A level of evidence was assigned to each intervention using a modified Sackett scale.Study Selection-The review included randomized controlled trials and non-randomized controlled trials which included prospective controlled trials, cohort, case series, case-control, prepost and post studies. Case studies were included only when there were no other studies found.Data Extraction-Data extracted included the PEDro or Downs and Black score, the type of study, a brief summary of intervention outcomes, type of pain, type of pain scale and the study findings.. Data Synthesis-Articles selected for this particular review evaluated different interventions in the pharmacological management of pain post SCI. 28 studies met inclusion criteria: there were 21 randomized controlled trials of these 19 had Level 1 evidence. Treatments were divided into five Conclusions-Most studies did not specify participants' types of pain; hence making it difficult to identify the type of pain being targeted by the treatment. Anticonvulsant and analgesic drugs had the highest levels of evidence and were the drugs most often studied. Gabapentin and pregabalin had strong evidence (five Level 1 RCTs) for effectiveness in treating post-SCI neuropathic pain, as did intravenous analgesics (lidocaine, ketamine and morphine) but the latter only had short term benefits. Tricyclic antidepressants only showed benefit for neuropathic pain in depressed individuals. Intrathecal baclofen reduced musculoskeletal pain associated with spasticity; however there was conflicting evidence for the reduction in neuropathic pain. Studies assessing the effectiveness of opioids were limited and revealed only small benefits. Cannabinoids showed conflicting evidence in improving spasticity related pain. Clonidine and morphine, when given together, had a significant synergistic neuropathic pain-relieving effect.

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mentioning

confidence: 99%

A Systematic Review of Pharmacologic Treatments of Pain After Spinal Cord Injury

Teasell

Mehta

Aubut

et al. 2010

Archives of Physical Medicine and Rehabilitation

150

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“…Similar to carbamazepine some results suggest that VPA inhibits sodium channel activation at high frequencies [209]. VPA also inhibits the activity of some enzymes [210] (Table 1).…”

Section: Valproic Acidmentioning

confidence: 83%

“…A leading hypothesis regarding how VPA exerts its anticonvulsant effects is by increasing the availability of GABA in GABAergic synapses [210]. GABA, an inhibitory amino acid neurotransmitter, would be expected to inhibit excessive firing of synapses, thus inhibiting epileptogenic activity.…”

Section: Valproic Acidmentioning

confidence: 99%

“…GABA, an inhibitory amino acid neurotransmitter, would be expected to inhibit excessive firing of synapses, thus inhibiting epileptogenic activity. A number of studies show that VPA, at therapeutic concentrations, is an inhibitor of succinate semialdehyde dehydrogenase (SSA-DH) [210][211][212][213][214]. This enzyme is critical for the GABA shunt, an enzymatic series of reactions that produces both glutamate and GABA by circumventing a portion of the tricarboxylic acid (TCA) cycle.…”

Section: Valproic Acidmentioning

confidence: 99%

“…Thus, GABA concentration would increase as GABA-T is inhibited by an increasing SSA concentration. Indeed, numerous studies have documented an increase in GABA concentration in rodent brain after VPA administration [210]. It is possible that VPA exerts its antimanic effects via inhibition of SSA-DH.…”

Section: Valproic Acidmentioning

confidence: 99%

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Mood stabilizer psychopharmacology

Gould

Chen

Manji

2002

Clinical Neuroscience Research

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Mood stabilizers represent a class of drugs that are efficacious in the treatment of bipolar disorder. The most established medications in this class are lithium, valproic acid, and carbamazepine. In addition to their therapeutic effects for treatment of acute manic episodes, these medications often are useful as prophylaxis against future episodes and as adjunctive antidepressant medications. While important extracellular effects have not been excluded, most available evidence suggests that the therapeutically relevant targets of this class of medications are in the interior of cells. Herein we give a prospective of a rapidly evolving field, discussing common effects of mood stabilizers as well as effects that are unique to individual medications. Mood stabilizers have been shown to modulate the activity of enzymes, ion channels, arachidonic acid turnover, G protein coupled receptors and intracellular pathways involved in synaptic plasticity and neuroprotection. Understanding the therapeutic targets of mood stabilizers will undoubtedly lead to a better understanding of the pathophysiology of bipolar disorder and to the development of improved therapeutics for the treatment of this disease. Furthermore, the involvement of mood stabilizers in pathways operative in neuroprotection suggests that they may have utility in the treatment of classical neurodegenerative disorders.

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