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

Several different drugs are now used, or are potentially useful, to treat patients with spasticity. Although these compounds vary in their actions on spinal neurons and reflex arcs, it is possible to formulate reasonable hypotheses regarding their modes of action. The benzodiazepines bind to specific benzodiazepine receptors linked to classic gamma-aminobutyric acid (GABA) receptors located on the terminals of primary afferent fibers. This binding results in an increased affinity of the GABA receptor for the amino acid, an augmented flux of chloride ions across the terminal membrane, and an increase in the amount of presynaptic inhibition. Baclofen activates GABAB receptors putatively located on the same terminals. Activation of these receptors retards the influx of calcium ions into the terminals, thereby reducing the evoked release of excitatory amino acids and possibly other transmitters. Progabide and its metabolites act on both classic and GABAB receptors. Glycine works on specific inhibitory receptors located on spinal interneurons and motoneurons. The phenothiazines act on the brainstem to alter the function of fusimotor fibers. Phenytoin and carbamazepine reduce the afferent output of muscle spindles. Dantrolene diminishes the activation of the contractile process in muscle fibers by reducing the release of calcium ions from the sarcoplasmic reticulum. This review summarizes the data supporting these concepts.
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PMID:Antispasticity drugs: mechanisms of action. 285 76

Progabide (PGB) is a gamma-aminobutyric acid (GABA)-agonist drug undergoing clinical evaluation for the treatment of spasticity, movement disorders, and epilepsy. Drug interactions were studied during a randomized, double-blind, crossover trial of the efficacy and toxicity of PGB in patients with partial seizures taking phenytoin (PHT) and carbamazepine (CBZ). In twenty-two of 32 patients (69%) receiving PGB, PHT dosage was reduced, while only four patients (12%) had their dosage reduced during placebo treatment (p less than 0.001). Carbamazepine dosage was decreased in five of 32 patients (16%) during the active treatment, while two patients (6%) had a dosage reduction when receiving placebo (p greater than 0.75). The mean PHT concentrations at the end of baseline, PGB, and placebo treatments were significantly different: 17.5, 20.4, and 16.8 mg/L, respectively (p less than 0.05). Nevertheless, careful adjustment of PHT dosage maintained serum concentration within +/- 25% of target values in both the PGB and placebo periods. Among patients who first received PGB and then placebo, PHT concentrations remained elevated relative to dose suggesting that PGB exerts a prolonged effect on PHT disposition. The addition of PGB to regimens including PHT results in a significant increase in serum PHT concentrations. This drug interaction most likely occurs as a result of PGB mediated inhibition of hepatic microsomal enzymes.
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PMID:Effect of progabide on serum phenytoin and carbamazepine concentrations. 342 61

Thirty-two patients with spasticity due to multiple sclerosis were entered into a randomized, double-blinded, placebo-controlled crossover trial of the gamma-aminobutyric acid agonist, progabide. Each patient was treated with a maximum of 45 mg/kg of progabide during each of two four-week treatment periods, separated by a two-week washout. Twenty-five participants completed the study; seven failed to complete the study due to adverse events. Progabide was associated with lessened spasticity. There was no loss of motor power associated with progabide. The physician, patients, and study nurse coordinator all declared preferences for progabide for treatment of spasticity. Ten participants (40%) chose to remain on progabide in an open, long-term follow-up protocol. Seven serious adverse events occurred. One consisted of fever and weakness without infection; the other six consisted of elevated aspartate aminotransferase and alanine aminotransferase levels, four of which were asymptomatic. All adverse events resolved entirely when the drug was stopped. Progabide is an effective antispastic agent and its antispastic effect is not accompanied by increased motor weakness. The use of the drug, however, is associated with a high incidence of adverse events, which will likely limit progabide's therapeutic usefulness.
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PMID:The GABA-agonist progabide for spasticity in multiple sclerosis. 363 75