Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cinnarizine and flunarizine are selective calcium blockers that have been used to treat and prevent vertigo. We studied 15 patients who had extrapyramidal syndromes after taking these drugs. Eleven patients had parkinsonism, one with persistent akathisia as well; one had an orofacial tremor; one, acute akathisia alone; and one an acute dystonic reaction. All but one improved when the drug therapy was discontinued. Seven patients were also depressed during treatment. Cinnarizine and flunarizine must therefore be added to the list of potentially risky drugs known to induce extrapyramidal reactions and depression.
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PMID:Flunarizine- and cinnarizine-induced extrapyramidal reactions. 357 97

1. Taenia preparations from the guinea-pig caecum yielded reproducible concentration-response curves to Ca2+ (EC50 134 +/- 8 mumol/1) when maintained in depolarizing Tyrode solution containing K+ (40 mmol/1). Drugs which are claimed to be "Ca2+ -antagonists" displaced the curves to the right without depression of the maximum response. In this test nifedipine, verapamil, diltiazem, pimozide, cinnarizine, flunarizine and fendiline appeared qualitatively similar but had different potencies. 2. The antagonist effects of nifedipine, verapamil and diltiazem were readily reversed by washout of the drugs from the bathing fluid, but the effects of the other drugs were not. 3. Cinnarizine, flunarizine, pimozide and fendiline were only weakly active as relaxants of Ca2+ (100 mumol/1)-induced contractions, when compared with their antagonist activity when applied initially in Ca2+ -free media. As the presence of Ca2+ (100 mumol/1) in the K+ -Tyrode reduced the antagonist effects of cinnarizine and pimozide, but not that of verapamil and diltiazem, the weak activity of some of the antagonists as relaxants of Ca2+ -induced contractions can be attributed to a protective effect of Ca2+ during the incubation period with the antagonist. 4. The problems associated with the assessment of the potency of drugs as "Ca2+ -antagonists" are discussed and it is proposed that three subgroups of drugs may exist within the overall classification.
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PMID:Assessment of "Ca2+ -antagonist" effects of drugs in K+ -depolarized smooth muscle. Differentiation of antagonist subgroups. 706 49

The temporal variation of HMG-CoA reductase activity in the liver and intestine of swine was investigated. The thin-layer chromatographic method widely used in the assay of the reductase was successfully applied to the porcine enzymes. Parallel circadian rhythms were demonstrated in both hepatic and ileal reductases from mash-fed animals. Peak activity occurred approximately 6 hr after feeding, 2.7-fold over the basal level in the liver, and 1.6-fold in the ileum. A milk-cholesterol diet caused a marked depression of both rhythms (90% in liver, 50% in ileum); however, the hourly variation in activity persisted in both organs. Cholestyramine was found to elevate hepatic activity (2.7-fold throughout the rhythm) without affecting that of the intestine. Clofibrate had no effect on either enzyme at any time during the cycle despite a 34% reduction in serum cholesterol concentrations.
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PMID:Circadian variation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in swine liver and ileum. 728 87

The effect of clofibrate (Atromid S, ethyl-2-(4-chlorophenoxy)-2-methylpropionate) administration for 7 days to rats on lipogenesis and on some lipogenic enzyme activities in brown adipose tissue (BAT), liver and white adipose tissue (WAT) was examined. As compared to control rats the rate of lipogenesis in BAT in the clofibrate-treated animals was significantly decreased. The rate of liver lipogenesis increased slightly, whereas lipogenesis in the WAT was not affected by clofibrate. In BAT, the drug treatment resulted in depression of fatty acid synthase, ATP-citrate lyase, malic enzyme, glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities. The activity of liver fatty acid synthase did not change, ATP-citrate lyase activity slightly decreased, whereas the activity of malic enzyme significantly increased in this organ after clofibrate feeding. The ATP-citrate lyase activity in WAT decreased, while fatty acid synthase and other lipogenic enzymes were not changed after clofibrate feeding. Clofibrate treatment did not influence the activity of NADP-linked isocitrate dehydrogenase and malate dehydrogenase (enzymes not linked directly to lipogenesis), either in BAT, liver or WAT. The data presented suggest that the hypolipidaemic effect of clofibrate in the rat may be due (possibly among other mechanisms) to reduction of the rate of fatty acid synthesis in BAT but not in the liver and WAT.
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PMID:Inhibition of lipogenesis in rat brown adipose tissue by clofibrate. 824 Apr 2

Cinnarizine, a piperazine derivative, is a widely prescribed medication for the treatment of vestibular disorders and motion sickness. Cinnarizine has antihistaminic, antiserotoninergic, antidopaminergic, and calcium channel-blocking properties. We present the first report in the English literature of cinnarizine poisoning and toxicokinetics. A 30-month-old toddler ingested 225 mg of cinnarizine, 18 times the recommended dose for older children. Four hours later, she became jittery with a wide-based gait and vomited 3 times. She was examined by her family physician, who reported stupor and twitching in both hands. On admission to the hospital, 6 hours after the ingestion, she was stuporous and had 3 short, generalized tonic-clonic convulsions that were controlled with a single dose of midazolam. Full clinical recovery was seen 10 hours after ingestion. Serum cinnarizine levels were 7407, 2629, and 711 ng/mL on admission and at 4 and 12 hours thereafter, respectively, 26.9 times higher than the therapeutic levels in adults. Elimination rate constant, calculated by linear regression of the ln concentrations of the 3 data points, was 0.19. Half-life, calculated from the equation t(1/2) = 0.693/kel, where kel is the elimination rate constant, was 3.65 hours. The manufacturing company revealed that their database contains 23 reports of cinnarizine overdose (adult and children), received between 1972 and 2004. Clinically, these cases reflect mainly symptoms of alterations in consciousness ranging from somnolence to stupor and coma, vomiting, extrapyramidal symptoms, and hypotonia. In a small number of young children, convulsions developed; recovery was uneventful in 4 cases and not reported in 1. The neurologic complication may be explained by the antihistaminic effect of cinnarizine because central nervous system depression and convulsions are known complications of antihistaminic overdose. It is hypothesized that cinnarizine-induced convulsions also are related to the antidopaminergic effect of the drug. Apart from the convulsions, no other adverse effects related to calcium channel-blocking properties, such as bradycardia or hemodynamic instability, were observed. Pediatric patients with cinnarizine overdose need to be observed in a health care facility for potential neurologic complications and be treated symptomatically. The delay to onset of clinical effect should be considered in the observation period.
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PMID:Pediatric cinnarizine overdose and toxicokinetics. 1663 15