Similar effects of a monoamine oxidase inhibitor and a sympathomimetic amine on memory formation

Amnesia resulting from inhibition of cerebral protein synthesis by cycloheximide can be prevented by subcutaneous injection of the monoamine oxidase inhibitor pargyline (25 mg/kg) or the sympathomimetic amine metaraminol (3.0 mg/kg) administered up to 30 min following learning of a single trial passive avoidance task in day-old chickens. The injection has to be made during the life time of labile memory for the prevention of cycloheximide-induced amnesia. On the other hand, amnesia induced by the Na/K ATP'ase inhibitor ouabain can only be prevented if these two agents are administered up to 5 min after learning, i.e. during the life time of short-term memory. In addition, both agents produce a retrieval deficit 90 min after the injection, but only when memory is in long-term storage. These results are compared to those obtained with administration of norepinephrine, d-amphetamine and diphenylhydantoin.     

Use of alpha-agonists for management of anaphylaxis occurring under anaesthesia: case studies and review

Anaphylaxis is an uncommon but serious complication of anaesthesia. Most current guidelines for the management of anaphylaxis list only epinephrine as a vasopressor to use in the event of cardiovascular collapse. We present two cases of anaphylaxis under anaesthesia where return of spontaneous circulation was refractory to epinephrine, but occurred following the administration of the alpha-agonist metaraminol. Potential advantages and disadvantages of using epinephrine in this setting, the role of alpha-agonists and some potential mechanisms accounting for their role in successful management are reviewed.     

Norepinephrine and metaraminol in septic shock: a comparison of the hemodynamic effects

Objective To compare the effects of norepinephrine and metaraminol on hemodynamics in septic shock patients.Design and setting Open-label, controlled clinical trial in the general intensive care unit of a university-affiliated hospital.Patients and participants Ten consecutive septic shock patients receiving norepinephrine to maintain the mean arterial pressure higher than 65 mmHg.Interventions Patients were monitored with pulmonary artery catheter and indirect calorimetry. At the baseline hemodynamic variables were obtained during norepinephrine infusion. Subsequently norepinephrine was replaced by metaraminol infusion in a dose sufficient to keep mean arterial pressure constant. After 20 min of stable arterial pressure a new set of measurement was repeated.Measurements and results Mean arterial pressure did not differ significantly with norepinephrine or metaraminol; there was no relationship between the norepinephrine and metaraminol doses. Replacement norepinephrine with metaraminol did not modify hemodynamic variables; in particular there were no changes in heart rate, stroke volume index, pulmonary artery occlusion pressure, or oxygen consumption index.Conclusions This study shows that metaraminol increases arterial pressure as does norepinephrine in septic shock patients. Despite similar effects of norepinephrine and metaraminol, there was no relationship between the dose of the two drugs.     

Improved stability and release control of levodopa and metaraminol using ion-exchange fibers and transdermal iontophoresis

Achievement of controlled drug delivery and stability of drugs during storage is a problem also in transdermal drug delivery. The objective of this study was to determine, whether an easily oxidized drug, levodopa, could be stabilized during storage using pH-adjustment and ion-exchange fibers. Controlled transdermal delivery of the zwitterionic levodopa was attempted by iontophoresis and ion-exchange fiber. Ion-exchange kinetics and transdermal permeation of a cationic (presumably more stable) model drug, metaraminol, were compared to the corresponding data of levodopa. Levodopa was rapidly oxidized in the presence of water, especially at basic pH-values. At acidic pH-values the stability was improved significantly. Ion-exchange group and the pH had a clear effect on the release of both the levodopa and metaraminol from the ion-exchange fiber. The adsorption/release kinetics of metaraminol were more easily controllable than the corresponding rate and extent of levodopa adsorption/release. Iontophoretic enhancement of drug permeation across the skin was clearly more significant with the positively charged metaraminol than with the zwitterionic levodopa. Ion-exchange fibers provide a promising alternative to control drug delivery and to store drugs that are degraded easily.     

On the mode of amine uptake by the Auerbach plexus of guinea pig small intestine

The uptake of the 2 erythro-isomers of metaraminol (l-MA, d-MA) by the Auerbach plexus of the guinea pig small intestine exhibits a Na⁺-dependency. Kinetic studies reveal that the effect of lowered [Na⁺] on l-MA uptake is to decrease V_maxwithout altering the apparent K_m, suggesting that a stoichiometric system is involved. The inhibitory effect of a high [K⁺] on l-MA uptake was examined kinetically and the results were similar to that seen upon lowering [Na⁺]. A comparison of the efficacy of desipramine to inhibit l-MA uptake at both 20.0 and 148.4 mM Na⁺ was undertaken and the drug was observed to be approximately 10 times less potent at the lowered [Na⁺]. The plot of d-MA uptake vs. [N⁺] resulted in a single linear function, whereas a similar plot for l-MA was biphasic. Reserpine, 18 hr after injection, had no effect on d-MA uptake but greatly decreased l-MA uptake in both normal conditions and low [Na⁺]. After reserpine, one phase of the l-MA uptake vs. [Na⁺] curve was abolished, resulting in a single linear function. The effect of reserpine on l-MA uptake is relatively short-lived as compared with the effect of the drug on endogenous catecholamine levels. Thus, 48 hr after injection, reserpine had no significant effect on l-MA uptake.     

间羟胺对大鼠心室肌细胞动作电位及L-型钙电流的影响

目的观察α肾上腺素能受体激动剂间羟胺对大鼠心室肌动作电位及L-型钙电流的影响。方法采用全细胞膜片钳方法,记录离体大鼠心室肌细胞动作电位和L-型钙电流。结果 200μmol/L间羟胺可使心室肌细胞L-型钙电流增大（P〈0.05）,动作电位时程（APD）明显延长（P〈0.01）,动作电位复极50%和90%时间（APD50and APD90）明显延长（P〈0.01）。100μmol/L酚妥拉明可使增大的的L-型钙电流和APD、APD50、APD明显恢复。结论间羟胺可明显延长大鼠心室肌动作电位时程,而酚妥拉明可不同程度地拮抗此效应。     

Release of 5-hydroxytryptamine from serotonergic nerve endings by alpha-methyl-meta-tyramine

Preparations of synaptosomes (P₂) from the telencephalon of the pigeon and rat were used to study the effects of α-methyl-m-tyramine (α-MMTA) and metaraminol on the efflux of radioactive serotonin (5-HT). The preparations were first incubated in the presence of 2.5 × 10^?8 M [³H]-5-HT to selectively label serotonergic nerve endings. Both α-MMTA and metaraminol in combination at a concentration of 0.15, 0.030 and 0.006 mM each significantly increased the efflux of [³H]-5-HT over control values in preparations from both the pigeon and rat. These two compounds together at the two concentrations also appeared to decrease the efflux of [³H]-5-hydroxyindoleacetic acid. At a concentration of 0.012 mM, α-MMTA significantly increased the efflux of [³H]-5-HT whereas metaraminol when tested alone at this concentration did not appear to have an effect on the release of [³H]-5-HT. The results are discussed in terms of the behavioral effects produced by α-methyl-meta-tyrosine in pigeons working on a multiple FR 50 FI 10 schedule of reinforcement.     

158例小儿重症肺炎的护理体会

目的探讨小儿重症肺炎的护理体会。方法选取我院在2006～2011年间收治的158例重症肺炎患儿,其中男孩80例,年龄在6个月～4岁之间,女孩78例,年龄在6个月～3岁,158例患儿均按照临床标准诊断为重症肺炎。将158例患儿随机分为两组,观察组84例,对照组74例,对两组患儿均进行纠正酸中毒及代谢紊乱、抗感染、对症等常规治疗以增加患儿的免疫能力,其中,观察组患儿在进行上述常规治疗的基础上再对患儿实行酚妥拉明、间羟胺的辅助治疗,再加以周到的护理,对于两组患者的病情改善情况进行跟踪观察,并对所得数据进行记录。结果经过一系列的治疗,两组患儿的病情均有不同程度的改善,其中观察组84例患儿,治愈26例,显效30例,有效18例,无效10例,有效率为88.1%,对照组74例患儿,治愈18例,显效22例,有效16例,无效18例,有效率为75.7%,两组患儿的病情改善情况差异显著,观察组的治疗效果要明显优于对照组的治疗效果,对于患儿病情的康复有较大帮助。结论在治疗小儿重症肺炎时,对患儿进行常规治疗后再加入酚妥拉明、间羟胺进行辅助治疗,再加上必要的周到护理,对于患儿病情的改善有较大的帮助,因此,值得在临床推广应用。     

GABA-mediated attenuation of noradrenaline release in the rat median preoptic area caused by intravenous injection of metaraminol

Previous studies have shown that the noradrenergic system in the median preoptic nucleus (MnPO) play an important role in the control of the body fluid balance and cardiovascular function and that the release of noradrenaline in the MnPO is regulated by gamma-aminobutyric acid (GABA) receptor mechanisms. The present study was carried out to examine whether the GABAergic system is involved in the modulation of the noradrenaline release in the MnPO in response to an elevation in blood pressure using in vivo microdialysis techniques. In urethane-anaesthetised male rats, the rise in arterial pressure caused by intravenous administration of the alpha-agonist metaraminol significantly decreased dialysate noradrenaline concentration in the MnPO area. The decrease in the noradrenaline level elicited by the metaraminol administration was significantly attenuated by perfusion with either bicuculline (10 microM), a GABA(A) receptor antagonist, or phaclofen (10 microM), a GABA(B) receptor antagonist, through a microdialysis probe. The amount of the antagonist-induced attenuation was much greater in the bicuculline-treated group than in the phaclofen-treated group. These results suggest that the release of noradrenaline in the MnPO area may be modulated by neural inputs from the peripheral baroreceptors, and that the neural inputs may be mediated in part through GABA(A) receptors rather than GABA(B) receptors in the MnPO area.     

Pharmacoepidemiology of metaraminol in critically ill patients with shock in a tertiary care hospital

BackgroundMetaraminol is increasingly used as a vasopressor in critically ill patients. Nevertheless, there remains limited evidence to support its use in international guidelines for management of shock.ObjectivesThe aim of the study was to describe the pharmacoepidemiology of metaraminol in critically ill patients with shock.MethodsA retrospective observational study was conducted in an intensive care unit (ICU) in Sydney, Australia. Patients admitted during a 1-year time frame who received metaraminol intravenous infusions for management of shock were included.ResultsA total of 152 patients were included. When metaraminol was used, it was the most common first-line vasopressor started for management of shock (97%, n = 147) and was used as monotherapy in 53% (n = 81) of patients. The median duration of metaraminol infusion in the ICU was 7 h (interquartile range [IQR] = 3 to 19), and the median maximum metaraminol infusion rate in the ICU was 4.0 mg/h (IQR = 2.5 to 6.0). Peripheral vasopressor infusions were used in 96% (n = 146/152) of patients for a median duration of 7 h (IQR = 2 to 18). In all these cases, the peripheral vasopressor used was metaraminol (100%, n = 146/146). Patients were commonly switched from metaraminol to noradrenaline infusions after insertion of a central venous catheter (R2 = 0.89). Patients treated with metaraminol monotherapy had a lower Acute Physiology and Chronic Health Evaluation III score (58 vs 68; median difference = −9, 95% confidence interval = −16 to −3; p < 0.01) and a shorter duration of overall vasopressor use in the ICU (12 vs 39 h, median difference = −24 h, 95% confidence interval = −31 to −18; p < 0.01) than those treated with combination vasopressors. No extravasation injury was reported in the study cohort.ConclusionsMetaraminol is often administered as a first-line peripheral vasopressor in the ICU and is used as a single agent in patients with lower severity of shock.