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)

It has been shown, in extensive animal experiments, that 1-(omega-dimethylaminoethylmethyl)-amino-3-phenylindole hydrochloride (binodaline HCl, Sgd-Scha 1059), can be regarded as an antidepressant with novel characteristics. With anticholinergic and histamine-antagonistic effects almost completely lacking, the main effects of binodaline HCl are to increase noradrenergic influences and to produce CNS depression. The acute toxicity of binodaline HCl is comparatively low, and the good tolerance has been demonstrated in long-term studies in laboratory animals.
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PMID:Pharmacological and toxicological studies of binodaline hydrochloride. 668 51

This study was designed to compare the direct actions of bupivacaine and lidocaine on the isolated perfused guinea pig Langendorff heart preparation. Sixty min after mounting, either bupivacaine HCl (0.3 or 3 micrograms/ml) or lidocaine HCl (10 or 30 micrograms/ml) was added to the perfusate, and the effect (if any) was compared to untreated control values 30, 60, and 90 min later. Although the highest concentrations of both drugs invariably produced statistically significant reductions in heart rate, df/dt, coronary blood flow, and myocardial oxygen consumption (MVO2), these reductions were consistently greater after bupivacaine. Moreover, arrhythmias occurred in 6 of 12 preparations in those hearts exposed to 3 micrograms/ml of bupivacaine. Most often these arrhythmias consisted of heart block and bi- or trigeminy. Additional studies indicated that the reduction in coronary blood flow and MVO2 produced by 3 micrograms/ml of bupivacaine was a consequence of its direct negative inotropic and chronotropic action. Although the myocardial depression produced by bupivacaine and lidocaine could be reversed readily by substituting fresh perfusate, increasing the extracellular calcium concentration in stepwise increments did not augment the negative inotropic or chronotropic effect produced by 3 micrograms/ml of bupivacaine or 10 micrograms/ml of lidocaine. We conclude that 3 micrograms/ml of unbound bupivacaine is more cardiotoxic than 30 micrograms/ml of unbound lidocaine in this model.
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PMID:Comparative cardiotoxicity of bupivacaine and lidocaine in the isolated perfused mammalian heart. 673 75

Exposure of mice to airborne sensory irritants causes a concentration-dependent depression of respiratory rate. The RD50 concentration (that concentration which elicits a respiratory rate decrease of 50%) has been predicted to be an unacceptable occupational exposure concentration due to intolerable sensory irritation and possible respiratory tract injury in humans. The purpose of this study was (1) to determine whether lesions occur in the respiratory tract of Swiss-Webster mice after exposure to the RD50 concentrations of ten sensory irritants and (2) to compare these changes with respect to type and severity. The RD50 values (ppm) of the chemicals studied are as follows: 2,4-toluene diisocyanate (0.4), acrolein (1.7), formaldehyde (3.1), chloropicrin (8.0), chlorine (9.3), sulfur dioxide (117), ammonia (303), hydrogen chloride (309), dimethylamine (511), and epichlorohydrin (687). After exposure of mice for 6 hr/day for 5 days, the respiratory tract was examined for histopathologic changes. All irritants produced lesions in the nasal cavity with a distinct anterior-posterior severity gradient. There was considerable variation in the extent, and nature of the lesions. The lesions ranged from slight epithelial hypertrophy or hyperplasia to epithelial erosion, ulceration, and necrosis with variable inflammation of the subepithelial tissues. Only chlorine, chloropicrin, and epichlorohydrin induced lesions in the lower respiratory tract. These findings give additional support to the potential value of the RD50 model for setting occupational exposure guidelines and predicting the risk of injury to the respiratory tract from exposure to airborne sensory irritants.
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PMID:Respiratory tract lesions induced by sensory irritants at the RD50 concentration. 674 Jun 88

The effects of oral methadone on respiration, ventilation, pupillary diameter, and plasma concentrations of estrone, estradiol, and progesterone were investigated in healthy nonpregnant women, 21 to 29 yr old. All women were in the follicular phase of the menstrual cycle. The study design was a randomized, double-blind, placebo-controlled trial. Six women received 15 mg methadone . HCl, and six received placebo. Alveolar ventilation and oxygen consumption before treatments correlated with plasma progesterone concentration (r2 = 0.85 and 0.68) but the slope and x-intercept of the ventilatory response to carbon dioxide curve did not. Female sex steroids in plasma were not affected by methadone. Mean elimination half-life of methadone from serum was 19 hr. Methadone-induced respiratory depression and miosis lasted more than 48 hr. The intensity of these changes was a linear function of the logarithm of the serum methadone concentration. Plasma progesterone concentration is an important determinant of resting ventilation and metabolism in the follicular phase of the menstrual cycle but endogenous progesterone does not protect women from the respiratory depressant effects of methadone.
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PMID:Respiratory and ventilatory effects of methadone in healthy women. 678 8

The effects of central administration of (D-Ala2)methionine-enkephalinamide (EA) on respiration were studied in the unanesthetized rat. EA induced a dose-dependent depression of respiratory rate and tidal volume which was reversed by the subcutaneous administration of naloxone HCl (10 mg/kg). Increasing atmospheric CO2 concentration stimulated EA-induced respiratory depression and the peptide produced a parallel shift to the right of both the respiratory rate -- PaCO2 and tidal volume -- PaCO2 curves. Following chronic administration of EA tolerance to the respiratory depression was observed and chronic exposure to morphine produced partial tolerance to the respiratory depression induced by EA. It was concluded that EA desensitizes the central chemoreceptors to CO2 and the action of EA on respiration parallels that of morphine.
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PMID:Characterization of the respiratory activity of (D-Ala2)methionine-enkephalinamide. 679 Feb 94

We have previously reported that hyperosmotic solutions of sodium chloride or of xylitol possess potent anti-ulcer activity and reduce gastric acidity in the rat. They also stimulate gastric prostaglandin (PG) biosynthesis, which may bear a causal relationship to the above effects. In the present investigation we studied the effect of intragastric hyperosmolarity on the transmucosal potential difference (PD) and on the permeability to H+ ions in the rat stomach. We also studied the effect of the prostaglandin synthetase inhibitors, indomethacin and flufenamic acid, on these parameters. Rat stomach was perfused in vivo, under urethane anesthesia, by xylitol solutions made up in 0.01 N HCl. While moderately hyperosmotic (13%) xylitol was without effect, the perfusion of intensely hyperosmotic xylitol (34.5%) resulted in a long lasting reduction of the transmucosal PD from a mean (+/- SEM) of -63 +/- 4 mV to a trough value of -40 +/- 3 mV. This depression of transmucosal PD was inhibited in a dose-related fashion by prior treatment with the PG-synthetase inhibitors. Acid recovery in the effluent was significantly reduced by the 34.5% xylitol solution and indomethacin pretreatment did not modify the effect of hyperosmotic xylitol. It is concluded that, although intensely hyperosmotic xylitol produces some of the characteristic effects of a barrier breaker, i.e. depression of transmucosal PD and acid back diffusion, these two phenomena probably involve different mechanisms, as indicated by their differential response to indomethacin.
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PMID:Hyperosmotic xylitol, prostaglandins and gastric mucosal barrier. 679 43

Two 14-day factorial experiments were performed to assess changes in growth, feed intake and urinary orotic acid excretion of weanling male Sprague-Dawley rats. The dietary variables investigated included the percentage of dietary casein in the basal diet, its supplementation with 5% lysine-HCl or 1% arginine-HCl and sucrose or two parts dextrin and one part sucrose as the only form of carbohydrate. The response to 5% supplemental lysine was strikingly similar to that seen with arginine-free diets. With 5% lysine added to 15% casein diets, growth decreased 25% and feed efficiency 20% while orotic acid excretion increased significantly. When 5% lysine was added to diets with 7.5 or 30% casein, these responses were smaller and were prevented by the simultaneous feeding of 1% arginine. Growth depression by lysine was partially reversed by replacing two-thirds of the dietary sucrose with dextrin. When unsupplemented, the casein diets containing only sucrose as carbohydrate supported less growth than the same diets containing the dextrin sucrose mixture. This difference was abolished by supplementation with 1% arginine, suggesting that sucrose increases arginine requirements for optimal growth. The data are consistent with the conclusion that orotic acid excretion is a useful index for determining when lysine excess is producing a functional deficiency of arginine.
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PMID:Orotic aciduria caused by feeding excess lysine to growing rats. 679 1

The induction and passive transfer of interferons have been shown to depress the level of cytochrome P-450 drug metabolism system of liver microsomes. Inducers of alpha or beta (Type I) interferons, such as Tilorone-HCl, statalon, mengovirus and others, suppressed the cytochrome P-450 system of rats or mice after administration. Induction of gamma (Type II) interferon also resulted in depression of the cytochrome P-450 system of mice. The gamma interferon was induced by sensitization of mice with Mycobacterium bovis strain BCG followed by challenge with tuberculin. The degree of depression of the cytochrome P-450 system correlated with the levels of interferon induced. In addition, passive transfer of exogenous gamma interferon also resulted in depression of the murine cytochrome-450 system. The metabolism of diphenylhydantoin, a drug metabolized by cytochrome-450, was examined in mice in which gamma interferon was induced. The metabolism of diphenylhydanoin was severely inhibited in mice which interferon was induced, and the level of inhibition correlated with the titer of gamma interferon induced. Passive transfer of gamma interferon also depressed the metabolism of diphenylhydantoin by murine cytochrome P-450.
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PMID:Effects of interferon on drug metabolism. 681 39

Local anaesthetic drugs were instilled into the pericardial sac of conscious rabbits through a chronically implanted catheter. Twenty mg of procaine HCl always caused complete blockade of cardiac vagal and sympathetic efferent nerves, tested by eliciting the baroreceptor-heart rate reflex, and abolished the reflex depression of renal sympathetic nerve activity elicited by impeding left ventricular outflow. It also slowed heart rate by a direct effect on the sinoatrial pacemaker. When the same dose of procaine was given intravenously there were only transient changes in blood pressure, heart rate and the baroreceptor-heart rate reflex. Lignocaine HCl and bupivacaine HCl were relatively less effective in blocking cardiac sympathetic efferent nerves. Intrapericardial procaine can be used in conscious animals to elucidate the part played by the cardiac receptor reflexes in control of the circulation.
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PMID:Blockade of cardiac nerves by intrapericardial local anaesthetics in the conscious rabbit. 688 93

Mice were treated with several different potentially carcinogenic components of tobacco smoke. The chemicals used were: 4-aminobiphenyl and aniline-HCl, which are found in high concentrations in sidestream tobacco smoke; hydrazine sulfate, which is found in high concentrations in mainstream tobacco smoke; and 2-methylquinoline, which is found in intermediate concentrations in both sidestream and mainstream smoke. The chemicals were injected i.p. into mice, and then alpha/beta interferon was induced in the mice by i.v. injection of polyriboinosinic-polyribocytidylic acid. The interferon was induced either 2, 24, or 48 hr after treatment with the tobacco smoke components. Mice treated with 4-aminobiphenyl showed some depression of interferon production 2 hr after treatment, maximum inhibition of interferon induction 24 hr after treatment, and a return to control levels of interferon 48 hr after treatment. Mice treated with hydrazine sulfate showed maximum inhibition of interferon induction 24 hr after treatment but no effects at any other treatment time. These components were the most carcinogenic chemicals of those utilized in this study. Treatment of mice with aniline-HCl, a chemical whose carcinogenic potential is still debated, resulted in marginal depression of interferon induction 24 hr after treatment. 2-Methylquinoline, the chemical with the lowest carcinogenic potential in this study, had no effect on interferon induction after administration to mice. In vivo interferon induction was, therefore, inhibited by treatment of mice with chemical carcinogens found in tobacco smoke. The efficacy of the chemical in inhibiting interferon induction was not influenced by the mainstream or sidestream smoke predominance of the chemical.
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PMID:Effect of carcinogenic components of cigarette smoke on in vivo production of murine interferon. 688 30


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