Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many therapeutic effects of benzodiazepines are mediated by neuronal high-affinity binding sites, i.e. benzodiazepine receptors (BR), located on GABAA receptors. Recently, endogenous BR ligands have partially been identified which, as agonists, either increase or, as inverse agonists, decrease GABAergic inhibition in the brain. BR antagonists, previously described as intrinsically inactive, induce effects in animals and humans under particular circumstances emphasizing a functional relevance of endogenous BR ligands. Several brain disorders, e.g. anxiety, insomnia, epilepsy, spasticity, alcoholism, coma, dementia, may be associated with a disequilibrium of opposing endogenous BR ligands changing the excitability of neurons implicated in aforementioned diseases. It is proposed that, depending on the relative role endogenous BR ligands play in the pathophysiology of these disorders, BR antagonists might demonstrate a variable efficacy in improving their symptomatology. In fact, such therapy would restore the homeostatic balance among various endogenous BR ligands being disturbed during an illness.
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PMID:Involvement of endogenous benzodiazepine receptor ligands in brain disorders: therapeutic potential for benzodiazepine antagonists? 747 87

Two cases of alcoholic cerebellar degeneration with pyramidal sign were reported. Patient 1 with alcohol dependence syndrome was a 46-year-old woman. After the alcohol abuse of about eight years, she complained of gait disturbance. The gait disturbance progressively worsened in about two months and she could not ambulate freely by herself. Neurological examination revealed nystagmus, ataxic and spastic gait, slight weakness and spasticity of the lower extremities, hyperreflexia of the extremities, bilateral Babinski's signs, and incoordination of the lower extremities. Examination of liver function and serum B12 was normal. Cranial CT scan and MRI revealed atrophy of the cerebellar vermis and dorsal part of the cerebellum. Though neurological signs slightly improved after the admission to our hospital and the abstinence from alcohol abuse, ataxic gait and hyperreflexia of the extremities have continued. Patient 2 was a 58-year-old man. He was a heavy drinker, but was not a patient with alcohol dependence syndrome. After the heavy drinking of about 40 years, he complained of gait disturbance. The gait disturbance had progressively worsened in about four months. Neurological examination revealed ataxic gait, hyperreflexia of the lower extremities, and bilateral Babinski's signs. Laboratory examination revealed slight liver dysfunction with minimal GPT and moderate gamma-GTP elevation. Examination of serum B12 was normal. Cranial CT scan and MRI revealed atrophy of the cerebellar vermis. Though bilateral Babinski's signs disappeared after the abstinence from heavy drinking, ataxic gait and hyperreflexia of the lower extremities have continued. Alcoholic myelopathy without hepatic cirrhosis was rarely reported. In the relation of alcoholic cerebellar degeneration to alcoholic myelopathy, our cases are interesting and important.
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PMID:[Alcoholic cerebellar degeneration with pyramidal sign--in relation to alcoholic myelopathy]. 847 68

The plant Cannabis sativa has a long history of medical use in the treatment of pain and spasms, the promotion of sleep, and the suppression of nausea and vomiting. However, in the early 70s cannabis was classified in the Narcotic Acts in countries all over the world as having no therapeutic benefit; therefore, it cannot be prescribed by physicians or dispensed by pharmacists. In the light of this contradictory situation an increasing number of patients practices a self-prescription with cannabis products for relieving a variety of symptoms. An anonymous standardized survey of the medical use of cannabis and cannabis products of patients in Germany, Austria and Switzerland was conducted by the Association for Cannabis as Medicine (Cologne, Germany). During about one year 170 subjects participated in this survey; questionnaires of 128 patients could be included into the evaluation. 68% of these participants were males, 32% females, with a total mean age of 37.5 (+/- 9.6) years. The most frequently mentioned indications for medicinal cannabis use were depression (12.0%), multiple sclerosis (10.8%), HIV-infection (9.0%), migraine (6.6%), asthma (6.0%), back pain (5.4%), hepatitis C (4. 8%), sleeping disorders (4.8%), epilepsy (3.6%), spasticity (3.6%), headache (3.6%), alcoholism (3.0%), glaucoma (3.0%), nausea (3.0%), disk prolapse (2.4%), and spinal cord injury (2.4%). The majority of patients used natural cannabis products such as marihuana, hashish and an alcoholic tincture; in just 5 cases dronabinol (Marinol) was taken by prescription. About half of the 128 participants of the survey (52.4%) had used cannabis as a recreational drug before the onset of their illness. To date 14.3% took cannabis orally, 49.2% by inhalation and in 36.5% of cases both application modes were used. 72.2% of the patients stated the symptoms of their illness to have 'much improved' after cannabis ingestion, 23.4% stated to have 'slightly improved', 4.8% experienced 'no change' and 1.6% described that their symptoms got 'worse'. Being asked for the satisfaction with their therapeutic use of cannabis 60.8% stated to be 'very satisfied', 24.0% 'satisfied', 11.2% 'partly satisfied' and 4.0% were 'not satisfied'. 70.8% experienced no side effects, 26.4% described 'moderate' and 3.3% 'strong' side effects. 84.1% of patients have not felt any need for dose escalation during the last 3 months, 11.0% had to increase their cannabis dose 'moderately' and 4.8% 'strongly' in order to maintain the therapeutic effects. Thus, this survey demonstrates a successful use of cannabis products for the treatment of a multitude of various illnesses and symptoms. This use was usually accompanied only by slight and in general acceptable side effects. Because the patient group responding to this survey is presumably highly selected, no conclusions can be drawn about the quantity of wanted and unwanted effects of the medicinal use of the hemp plant for particular indications.
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PMID:[Results of a standardized survey on the medical use of cannabis products in the German-speaking area]. 2146 33

gamma-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system. GABA is converted from glutamic acid by the action of glutamic acid decarboxylase (GAD) of which two isoforms exist GAD65 and GAD67. GABA then is broken down, both within the cell and in the synaptic cleft by GABA transaminase to form succinic semialdehyde. In turn, succinic semialdehyde is converted either to succinic acid by succinic semialdehyde dehydrogenase or into gamma-hydroxybutyric acid (GHB) by succinic semialdehyde reductase. Because GABA modulates the majority of inhibition that is ongoing in the brain, perturbations in GABAergic inhibition have the potential to result in seizures. Therefore, the most common disorder in which GABA is targeted as a treatment is epilepsy. However, other disorders such as psychiatric disease, spasticity, and stiff-person syndrome all have been related to disorders of GABAergic function in the brain. This review covers the roles of GABAergic neurotransmission in epilepsy, anxiety disorders, schizophrenia, stiff-person syndrome, and premenstrual dysphoric disorder. In the final section of this review, the GABA metabolite GHB is discussed in terms of its physiological significance and its role in epilepsy, sleep disorders, drug and alcohol addiction, and an inborn error of GABA metabolism, succinic semialdehyde dehydrogenase deficiency.
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PMID:GABA, gamma-hydroxybutyric acid, and neurological disease. 1289 48

Baclofen is a gamma amino butyric acid (GABA) derivative that is a specific agonist at GABA-B receptors. Initially used in the treatment of spasticity, it is now being used in the treatment of alcohol dependence. Although it has several known adverse effects, incidence of rashes developing due to baclofen is very rare, and morbiliform rashes due to baclofen, an exceedingly rare adverse effect, has been reported only once before. We report a case series of 4 patients who developed morbiliform rashes after initiation of baclofen.
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PMID:Baclofen-induced morbiliform rashes: a case series. 2111 92

Baclofen, a very potent agonist of the GABA system, has anti-craving properties that can provide to this old drug, usually prescribed against spasticity, a new interest in the treatment of alcoholism. Baclofen suppresses the craving, while other anticraving medications reduce it. This suppression is dose-dependent and appears at doses 3 mg/kg/d. Most of the studies with human beings used much lower doses, often 30 mg/day. At this dosage, baclofen is associated with outcome similar to other anticraving medications. A published self case-report using high dose of baclofen suggests the suppression of craving on a prolonged period of time. This publication gave a new dynamic to the prescription of high doses of this drug. Currently, no studies provide robust results on the efficacy of high dosages while some clinicians prescribe baclofen to treat patients who have failed in prior treatments.
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PMID:[Baclofen: the new miracle cure for alcoholism?]. 2183 11

Baclofen is approved for muscle spasms and cerebral spasticity. Several studies have recently investigated the use of baclofen for alcohol withdrawal symptoms and as an abstinence-promoting agent in alcohol-dependent subjects. The evidence is too weak to recommend baclofen for alcohol withdrawal, and drugs with better documentation such as benzodiazepines and carbamazepine should be preferred for this indication. The evidence for the use of baclofen to prevent relapse to drinking in alcohol dependence is somewhat conflicting, but the drug could be considered as a therapeutic option in case of conservative measures and approved drugs such as disulfiram and acamprosate having insufficient effect. Despite enthusiastic appraisal in case reports, the use of baclofen in high doses to suppress alcohol craving cannot be recommended due to insufficient evidence. Trials that may resolve this issue are underway.
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PMID:[Baclofen for alcohol addiction]. 2204 11

Alcohol dependence is a severe, chronic illness. Even the best-assessed drugs used to maintain abstinence are poorly effective. Some patients remain dependent after several treatment attempts. Baclofen has been tested for its capacity to reduce craving for alcohol. We reviewed the data available as of early 2013, using the standard Prescrire methodology, in order to assess the harm-benefit balance of baclofen in maintaining abstinence or moderation in alcohol-dependent patients. Two double-blind, randomised, placebo-controlled trials conducted by the same team tested baclofen 30 mg/day in 123 alcohol-dependent patients referred to alcohol treatment centres. After 1 or 3 months of followup, more patients remained abstinent in the baclofen group than in the placebo group. In another double-blind, randomised trial, baclofen 30 mg/day was not more effective than placebo in 80 alcohol-dependent patients recruited through advertisements, many of whom were seeking treatment for the first time. Three uncontrolled retrospective series reported the results obtained in 300 alcohol-dependent patients, most of whom were in treatment failure. They were treated with high, escalating doses of baclofen (on average about 150 mg per day, up to 400 mg per day) with the intention of reducing their craving for alcohol. After 3 to 24 months of follow-up, about half of the patients reported moderate or zero alcohol consumption. At moderate doses, baclofen has been used since the 1970s in the treatment of certain forms of muscle spasticity. The main adverse effects reported in this setting were drowsiness (especially early during treatment) and various neuropsychiatric disorders such as dizziness, euphoria, depression, headache, paraesthesias, speech disorders, ataxia and insomnia. The adverse effects of high-dose baclofen are mainly based on monitoring of hundreds of alcohol-dependent patients, 69 reports to French pharmacovigilance centres in 2011, and cases of overdose or accidental ingestion reported to French poison control centres. Confusion and mania were reported, and coma occurred with doses of 200 mg or more. Some data point to an increased risk of suicide. In practice, in early 2013, more data are needed on the efficacy and adverse effects of baclofen in alcohol dependence, compared with other options. Patients who have received thorough, well-balanced information, and decide to try baclofen as a last resort should be included in comparative clinical studies.
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PMID:Baclofen and severe alcohol dependence: an uncertain harm-benefit balance as of early 2013. 2417 Dec 18

Since CXCL12 and its receptors, CXCR4 and CXCR7, have been found in the brain, the role of this chemokine has been expanded from chemoattractant in the immune system to neuromodulatory in the brain. Several pieces of evidence suggest that this chemokine system could crosstalk with the GABAergic system, known to be the main inhibitory neurotransmitter system in the brain. Indeed, GABA and CXCL12 as well as their receptors are colocalized in many cell types including neurons and there are several examples in which these two systems interact. Several mechanisms can be proposed to explain how these systems interact, including receptor-receptor interactions, crosstalk at the level of second messenger cascades, or direct pharmacological interactions, as GABA and GABAB receptor agonists/antagonists have been shown to be allosteric modulators of CXCR4. The interplay between CXCL12/CXCR4-CXCR7 and GABA/GABAA-GABAB receptors systems could have many physiological implications in neurotransmission, cancer and inflammation. In addition, the GABAB agonist baclofen is currently used in medicine to treat spasticity in patients with spinal cord injury, cerebral palsy, traumatic brain injury, multiple sclerosis, and other disorders. More recently it has also been used in the treatment of alcohol dependence and withdrawal. The allosteric effects of this agent on CXCR4 could contribute to these beneficial effects or at the opposite, to its side effects.
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PMID:CXCL12 chemokine and GABA neurotransmitter systems crosstalk and their putative roles. 2480 25

Used in the treatment of spasticity at low doses, baclofen is also prescribed off-label at high doses for the treatment of alcohol dependence. Several cases of baclofen intoxication have been reported, but only 1 case deals with the treatment of alcohol dependence. Thus, we report the first death in the context of baclofen off-label use of an alcohol-dependent patient with a high blood baclofen concentration after intentional drug intoxication. The safety profile of baclofen in the treatment of alcohol dependence is reviewed and discussed, underlining the obligatory caution that may support any prescription of high doses of baclofen in this off-label indication and especially in patients with concomitant psychiatric disorders.
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PMID:Death of an alcohol-dependent patient following intentional drug intoxication: implication of baclofen? 2530 Jul 47


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