UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1 Differentiation of the roles of histamine H1- and H2-receptors in the mediation of the effects of histamine on the isolated working heart of the guinea-pig was achieved through the use of histamine and selective histamine receptor agonists and antagonists. 2 Histamine over the dose range 10(-9) mol to 10(-6) mol produced dose-related increases in sinus rate, left intraventricular pressure (LVP)max, LVdP/dtmax, coronary flow, aortic flow, total cardiac output and external pressure-volume work. 3 Dimaprit, a selective histamine H2-receptor agonist, produced very similar responses to histamine. 4 2-Pyridylethylamine, a selective histamine H1-receptor agonist, had little effect on cardiac function unless large doses were administered. Such doses produced increases in all measured parameters. 5 Cimetidine, a selective histamine H2-receptor antagonist, antagonized the effects of histamine and dimaprit and some but not all effects of 2-pyridylethylamine. In the presence of cimetidine a decrease in all parameters with the exception of sinus rate was observed with both histamine and 2-pyridylethylamine. 6 The selective histamine H1-receptor antagonist, mepyramine, had little effect on responses to all three agonists. However, the depressant effects observed with histamine and 2-pyridylethylamine in the presence of cimetidine were antagonized by mepyramine. 7 The results indicate the important role of the histamine H2-receptor in the mediation of the gross cardiac effects of histamine and also indicate that histamine H1-receptors can mediate cardiac depression.
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PMID:Differentiation of the roles of histamine H1- and H2-receptors in the mediation of the effects of histamine in the isolated working heart of the guinea-pig. 3 43

Cimetidine, ranitidine and famotidine are antagonists of the histamine H2-receptors on the spontaneously beating right atrium of the guinea pig. When analyzed by the classical Schild method their pA2-values are respectively: 6.3, 6.8 and 7.7 with dimaprit as agonist and 5.8, 6.5 and 7.7 with histamine as agonist. Radioligand-displacement studies with [3H]-tiotidine as radioligand resulted in pKd values for cimetidine, ranitidine and famotidine of 6.3; 6.9 and 8.2 respectively. In dimaprit-stimulated atria all antagonists added at concentrations above their Kd values depressed the maximal increase in frequency. In the presence of histamine this effect was much less pronounced and only visible at concentrations of ranitidine and famotidine around 10.Kd. The rightward shift of the curves as well as the decrease in Emax are reversible but the dissociation constants of the antagonists are small (less than 10(-3) s-1). The spontaneously beating right atrium showed receptor reserve for histamine and virtually no receptor reserve for dimaprit. The results have been interpreted in a model in which H2-antagonists act mainly by competing with the agonist for the histamine receptor site but have in addition a distinct affinity for a secondary site on the receptor. Occupation of this site by the antagonist prevents building up of the stimulus elicited by the agonist and thus decreases the Emax. In systems with receptor reserve (histamine) the effect of antagonist binding to the secondary binding site is seen only at high concentration of antagonist while in absence of receptor reserve (dimaprit) the depression of Emax is directly visible. Simulations of the model show that the affinity of this secondary binding site is 50-(famotidine) to 100-(cimetidine and ranitidine) fold lower than for the agonist binding site.
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PMID:Mechanism of action of H2-antagonists on histamine- or dimaprit-stimulated H2-receptors of spontaneously beating guinea-pig atrium. 170 83

Oral administration of the antiulcerogenic drug, cimetidine, was studied on kidney-bound hydrolytic enzymes at three different dose levels (30 mg, 100 mg, and 2000 mg/kg body weight) and for single administration for 2 and 24 h, and daily administration for 15 days in mice. It significantly inhibited Na+, K(+)-ATPase, Mg(2+)-ATPase, and Ca2+, Mg(2+)-ATPase in the isolated basolateral membrane (BLM). Brush-border-membrane-(BBM)-associated enzymes, sucrase, lactase, maltase, leucine aminopeptidase, and alkaline phosphatase also showed a marked reduction. Substrate saturation kinetics revealed the nature of inhibition was of mixed type in the case of sucrase, lactase, maltase, and alkaline phosphatase (Km was increased, while Vmax decreased), whereas it was of non-competitive type for leucine aminopeptidase (Km was unchanged, while Vmax decreased). In vitro addition of cimetidine (5-20 mM) to the BBM also inhibited the enzyme activity. Dixon plot produced the inhibition constant (Ki) for cimetidine in the case of maltase, alkaline phosphatase, and leucine aminopeptidase in the order of 14.83, 32.83 and 11.5 mM, respectively. Analysis of lipids revealed a significant reduction in BBM-associated phospholipid and phospholipid/cholesterol molar ratio, while the neutral lipid fraction, i.e., cholesterol and triglycerides were not altered. Free fatty acid exhibited an increase after drug treatment, which was significant at higher dose after 24 h of single and 15 days of daily treatment. BLM-associated lipids did not exhibit any significant change. Cimetidine-induced depression in renal BLM- and BBM-associated disaccharidases and ATPases, at least at the higher dose level, may have serious consequences in the absorption of end-product nutrients.
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PMID:Depression of membrane-bound hydrolases by cimetidine in mouse renal basolateral and brush border. 183 34

Ganglionic effects of the histamine H2 receptor antagonists cimetidine, ranitidine and 1-nitro-2-(2-propynylamino)-2-(2-[dimethylaminomethyl-2-furanyl) methylthiol]-ethylamino)ethylene (ORF 17578) were compared in the isolated superior cervical ganglion of the rat. Extracellular recording of compound action potentials showed that the drugs caused concentration-dependent inhibition of ganglionic transmission, as indicated by depression of the postganglionic compound action potential. Cimetidine-induced inhibition of ganglionic transmission was stimulus frequency-dependent. Increasing the Ca2+ from 2.2 to 4.4 mM in the bathing solution did not significantly affect the inhibitory actions of these agents. In the series with ranitidine, pretreatment with DFP to inhibit acetylcholinesterase similarly had no significant effect on the depression of the compound action potential by ranitidine. All three agents had little or no effect on nerve conduction in isolated vagi of the rat. The results indicate that all three histamine H2 receptor blockers inhibited ganglionic transmission, but only in large concentrations. The results also suggest that the blocking effect of these drugs was unrelated to their reported anticholinesterase action or to blockade of histamine H2 receptors, which are believed to exist on the presynaptic membrane. It is suggested that the ganglion effect may be due to the action of these agents on the acetylcholine receptor-ion channel complex in the postsynaptic membrane.
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PMID:A comparative study of the actions of histamine H2 receptor antagonists on transmission in the isolated superior cervical ganglion of the rat. 197 Jan 32

Responses of the toad isolated rectus abdominis muscle to cumulative doses of acetylcholine were recorded in the absence or presence of varying concentrations of cimetidine, ranitidine or oxmetidine. The corresponding cumulative log concentration-response curves for acetylcholine were then plotted for each antagonist studied. Cimetidine (5 mmol/l), ranitidine (1 mmol/l) and oxmetidine (0.02 mmol/l) potentiated the effect of acetylcholine by 4-fold, 2.6-fold and 1.3-fold, respectively. At higher concentrations all three histamine H2-receptor antagonists produced a concentration-dependent and non-parallel shift of the acetylcholine curve to the right of the corresponding control curve accompanied by a depression of the maximal response. The results provide further evidence that the H2-antagonists studied possess anticholinesterase activity and also suggest that the H2-antagonists may produce neuromuscular blockade by ion-channel block. The clinical implications of the results obtained are also discussed.
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PMID:Anticholinesterase activity of and possible ion-channel block by cimetidine, ranitidine and oxmetidine in the toad isolated rectus abdominis muscle. 241 17

Many drugs potentiate the action of non depolarizing relaxants. These interactions are of clinical importance if such drugs are administered during the perioperative period. H2 Antagonists are increasingly often used for premedication. Cimetidine inhibits the elimination of a number of drugs used in the perioperative period. We therefore investigated whether H2 antagonists enhanced neuromuscular blockade by vecuronium, a medium short acting non depolarizing muscle relaxant. METHODS. The study was carried out in 24 female patients (ASA class I or II) scheduled for microsurgical procedures. Neuromuscular transmission was recorded electromyographically using four stimulations every 20 s to the ulnar nerve. After induction with thiopentone, anesthesia was maintained with fixed concentrations of volatile anesthetics. Fentanyl was administered for additional analgesia. Vecuronium was used as the sole muscle relaxant. Fixed repetitive doses of vecuronium (0.8-1.2 mg) were injected whenever the T1 returned to 25%. This time interval was defined as the T1-25 period. The study proper started when the T1-25 period had stabilized. After two control periods, six patients in each group received either 200 or 400 mg cimetidine or 100 mg ranitidine. The fourth group was the control group. The T1-25 periods and the maximal EMG depression were recorded automatically for at least two further periods. The first measured period was recorded as 100% and the length of each other periods was calculated as a percentage of the control period. This method enables an intraindividual comparison of the length of the T1-25 period and the maximal EMG depression before and after administration of the H2 antagonists. A two-tailed Student's t-test was used to test statistical significance, P less than 0.05 being accepted as significant. RESULTS. In the control group and in the group with 200 mg cimetidine or 100 mg ranitidine no statistical significant prolongation of the T1-25 period or of the maximal EMG depression could be observed, while after 400 mg cimetidine there was significant prolongation (mean 161 +/- 14.8%) of the T1-25 period and significantly greater EMG depression compared with the pre-cimetidine values. In the groups with 200 mg cimetidine or 100 mg ranitidine few patients showed prolongation of the T1-25 period up to 130%. DISCUSSION. Our results confirm experimental studies that have shown cimetidine to enhance aminoglycoside--relaxant interactions. Because we found an immediate response to the administration of the H2 antagonists, the interaction cannot be on the elimination side; it must be at the neuromuscular junction. Experimental investigation has shown that calcium reverses the cimetidine effects. It is therefore probable that the cimetidine--relaxant interaction occurs at the presynaptic level. Careful observation seems to be necessary if H2 antagonists, especially cimetidine, are administered intraoperatively at the same time as drugs that also enhance
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PMID:[Interactions of H2 antagonists and non-depolarizing muscle relaxants]. 256 80

The role of the vagus nerve and adrenoceptor stimulation in acid secretion after pylorus-ligation in the rat has been examined. All drugs were administered intraperitoneally. Atropine (5 mg kg-1) depressed the H+ output (111 mumols +/- 33.8 vs 412.5 mumols +/- 62.2, mean +/- s.e.m., n = 10, P less than 0.001); cimetidine (40 mg kg-1) did not enhance this action, while vagotomy was more effective than atropine (32.7 mumols +/- 4.9, mean +/- s.e.m., n = 10, P less than 0.05). Atropine (10 mg kg-1) produced a similar depression to the 5 mg kg-1 dose. Cimetidine (100 mg kg-1) depressed the H+ output (248.5 mumols +/- 46.8, mean +/- s.e.m., n = 10, P less than 0.05). Propranolol (5-20 mg kg-1) had no significant effect on the H+ output but dose-dependent inhibition was produced by phenoxybenzamine or phentolamine; an inhibition similar to that achieved by vagotomy was seen with the 20 mg kg-1 dose. Both these drugs (5 or 10 mg kg-1) had no significant effect on the H+ output when given with atropine (5 mg kg-1) but the H+ output was significantly lower than that produced by either drug at the same dose given alone. Atropine (5 mg kg-1) with phenoxybenzamine or phentolamine (20 mg kg-1) produced H+ output not significantly different from that with vagotomy or either alpha-adrenoceptor given alone at 20 mg kg-1, but the result was significantly (P less than 0.05) lower than the H+ output with atropine (5 mg kg-1) alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of vagal adrenergic activity in the mechanism of gastric acid secretion after pylorus-ligation in the rat. 257 4

The most widely used H2-receptor antagonist, cimetidine, is known to interact with cytochrome P-450 drug-metabolizing enzymes and, therefore, interacts with other drugs which may be administered concurrently. In this study, effects of three H2-receptor antagonists, famotidine, ranitidine, and L-643,441, on drug interaction were studied using cimetidine as a positive control. Cimetidine and L-643,441, but not famotidine or ranitidine, prolonged antipyrine elimination and hexobarbital-induced sleeping time. The effect of cimetidine and famotidine on the anticoagulant effect on warfarin in rats was also investigated. Pretreatment of rats with cimetidine produced a significant depression of plasma prothrombin complex activity, whereas concomitant administration of famotidine did not alter the plasma prothrombin complex activity. Whereas cimetidine is known to impair the elimination of a number of drugs metabolized by microsomal mixed function oxidase enzyme systems, the results of the present study suggest that famotidine and ranitidine have little effect on these enzyme systems.
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PMID:Comparative effects of H2-receptor antagonists on drug interaction in rats. 287 21

Psychiatric disorders induced by drugs are of most concern when they occur in the context of therapeutic use of a drug. Such iatrogenic psychiatric disturbances may interfere considerably with the treatment of the primary illness and may cause concern to patients, their relatives and the medical staff. Because many drugs are often used simultaneously in seriously ill patients, it may be difficult to be sure which drug may have been responsible. The best procedure is to remove those drugs which are most probable causes of the psychiatric disturbances as well as any drugs that are not truly essential for the treatment of the patient. Problems involved in evaluating the relationship between use of drugs and psychiatric disorders are considerable. Many reports are isolated cases and the denominators which might provide some idea of the potential risk are unknown. Many relationships are still controversial, such as the association of depression with sedatives, antihypertensives and oral contraceptives. Areas of uncertainty are great. Psychomotor impairment may be caused by a drug that can alter consciousness, or any drugs that can produce more delineated psychiatric syndromes. Sedative drugs are those most commonly associated with psychomotor impairment, and may include psychotherapeutic drugs, sedative antihistamines, narcotic analgesics and, of course, the widely used social drug, alcohol. Delirious states are most often associated with drugs that possess central anticholinergic actions. These include not only drugs clearly identified as anticholinergics, but also tricyclic antidepressants and anti-Parkinson drugs. Cimetidine, which is often used parenterally in seriously ill patients, is also a prominent cause. Delirium is most often seen in elderly patients and in those who have received rather large doses of drugs. The association of schizophrenic-like psychoses with dopaminomimetic drugs tends to support the prevailing dopamine hypothesis of schizophrenia. Levodopa, the dopamine precursor, and bromocriptine, a direct dopamine agonist, are examples of such relationships. Abuse of social drugs has also been thought to provide a useful model of schizophrenia. Hallucinogens are probably a rather poor model, abuse of amphetamines may provide a better model, and possibly the best is the psychotic state elicited by phencyclidine. Manic reactions are clinically difficult to differentiate from schizophrenic-like psychoses and are often produced by similar drugs. Corticosteroids may produce either manic or schizophrenic-like disorders, as well as occasionally confusion and depression.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Drug-induced psychiatric disorders and their management. 354 May 20

The kinetics and dynamics of single doses (5 mg p.o.) of the optical isomers of acenocoumarol (R-AC and S-AC) were followed in healthy subjects and the effect on them of cimetidine 800 mg/day was also investigated. The AC enantiomers differed greatly in their pharmacokinetics. The mean residence time (MRT) of R-AC was about 10 times longer than that of S-AC, 15 h vs 1.2 h. There was no difference in the volume of distribution. Depression of blood clotting activity (Thrombotest) was observed only after administration of R-AC. The inactivity of S-AC as a vitamin K antagonist must be ascribed to its short MRT. Cimetidine did not affect the acute oral kinetics of R- and S-AC, nor did it affect the anticlotting activity of R-AC. The urinary excretion pattern of the 6- and 7-hydroxylated AC metabolites was not altered during cimetidine treatment. Although the present studies showed no effect of cimetidine on the pharmacokinetics and dynamics of acenocoumarol, the findings of Serlin et al. suggest that cimetidine should not be administered during acenocoumarol therapy.
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PMID:Lack of effect of cimetidine on pharmacodynamics and kinetics of single oral doses of R- and S-acenocoumarol. 375 50

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