Ventricular dysrhythmias following an alfentanil anesthetic in a patient on reserpine for hypertension

The case is presented of a hypertensive patient on reserpine, who developed ventricular irritability after administration of alfentanil, a new ultra-short-acting narcotic used in anesthesia. The dysrhythmias resolved after cessation of the offending agent. There are no reported cases of interaction of reserpine and alfentanil in the literature.     

DILTIAZEM AND VERAPAMIL LOWER BLOOD PRESSURE IN THE UNANAESTHETIZED RAT THROUGH CNS MECHANISMS INVOLVING ENDOGENOUS OPIOIDS

1. To evaluate and compare the effects of the calcium channel blockers, diltiazem and verapamil, on CNS modulation of blood pressure, unanaesthetized and unrestrained rats with catheters previously inserted into the lateral cerebral ventricle and femoral artery received intracerebroventricular (i.c.v.) administration of diltiazem or verapamil, 10 or 50 micrograms/kg, or their diluent. 2. Diltiazem, at both 10 and 50 micrograms/kg i.c.v., produced significant (P less than 0.05) decreases in systolic and diastolic blood pressure and heart rate. Verapamil, at 50 micrograms/kg but not at 10 micrograms/kg i.c.v., produced a significant (P less than 0.05) decrease in blood pressure, while both doses significantly (P less than 0.05) decreased heart rate. 3. To examine the endogenous opioid systems as potential modulators of the effects of these calcium antagonists, the mu opioid antagonist naloxone, 20 micrograms/kg, was administered i.c.v. either before or after each calcium antagonist. Naloxone reversed and prevented the reduction in blood pressure produced by both agents. The decrease in heart rate produced by verapamil but not diltiazem was reversed by naloxone. 4. The results suggest that: (1) calcium channels in neuron membranes in the CNS play a role in blood pressure regulation; (2) at least part of the blood pressure reduction produced by calcium blockers may be effected in the CNS; and (3) central opioid mechanisms modulate part of the action of the calcium antagonists verapamil and diltiazem on blood pressure.     

1H-n.m.r. investigation of conformational features of cyclic,penicillamine-containing enkephalin analogs

Conformational features of a series of cyclic, penicillamine-containing enkephalin analogs, all of which display selectivity for the delta opioid receptor, were studied by ¹H n.m.r. in aqueous solution. Comparison of chemical shifts, coupling constants, and temperature dependence of amide proton chemical shifts suggests different conformational features among the analogs, some of which can be related to the different primary sequences of these peptides. The observation that some of the analogs display disparate individual conformational features while exhibiting similar opioid potency and receptor selectivity suggests that such analogs may share a similar overall topography or at the least maintain the same relative orientations of key portions of the molecule.     

The ‘Hyperactive’ Child

A new, more apt designation, attentional deficit disorder (ADD), may help dispel some of the myths that have surrounded the “hyperactive” child. An abnormally high level of physical activity is a common but not universal finding in these children but is not their central problem. In most affected children, early diagnosis and specific drug treatment can ward off the often disastrous psychiatric and social consequences of ADD.     

纳洛酮在乙型脑炎治疗中的意义

目的 :研究乙脑的发病与内源性阿片肽的关系 ,以及阿片肽拮抗剂纳洛酮治疗乙脑的机制和疗效。方法 :治疗组 5 6例应用纳洛酮 0 .0 2mg (kg·次 ) ,每 6～ 8h 1次 ,3～ 5d ;对照组 5 0例未用 ,余治疗相同。观察疗效 ,同时检测急性期和恢复期的血浆和CSF内源性阿片肽含量。结果 :治疗组疗效显著 ,且急性期时血浆和CSF内源性阿片肽明显高于正常值 (P <0 .0 1 ) ,至恢复期时显著下降 (P <0 .0 1 ) ,治疗组比对照组下降更明显。结论 :乙脑的发病与内源性阿片肽释放增加有关 ,纳洛酮治疗后可使内源性阿片肽下降 ,是治疗乙脑的有效药物之一。     

阿片类药物透过血脑屏障的三维构效研究

目的:建立药物透过血脑屏障的三维构效模型,为药物分子设计提供理论依据。方法与结果:利用比较分子力场分析方法建立了阿片类药物透过血脑屏障的三维定量构效模型,该模型有较高的预测能力,交叉验证系数r²_cv=0.718,相关系数r²=0.978,F₃,7=67.902,标准偏差SE=0.209。结论:根据CoMFA模型系数等势图,解释了该类药物透过血脑屏障的构效关系。     

Antinociceptive interactions of mu- and kappa-opioid agonists in the colorectal distension assay in rats

Interactions of opioid agonists, fentanyl and oxymorphone (mu-selective) and spiradoline and enadoline (kappa-selective), were examined for additive, sub-additive, or supra-additive antinociception in the colorectal distension (CRD) assay. Single-dose values (mg/kg, 0.006-0.016 for fentanyl, 0.25-1.26 for spiradoline, etc.) were summed to formulate theoretical additive-dose plots for comparison with actual combined-dose effects. Combined fentanyl and spiradoline yielded additive (low-dose levels) or supra-additive (high-dose levels) effects. Single and combined doses of fentanyl (0.012 mg/kg) and spiradoline (0.3 mg/kg) were tested after pretreatment with saline, beta-funaltrexamine (b-FNA, mu-selective antagonist), or nor-binaltorphimine (n-BNI, kappa-selective antagonist). Supra-additive effects of combined agonists were attenuated by either antagonist (greater with n-BNI). But paradoxical patterns of antagonism of single-dose effects occurred: the fentanyl antinociception was not antagonized by b-FNA, whereas the spiradoline antinociception was. The results indicate complex interactions of agonists in this visceral pain model and potential for combined agonists to improve pain relief with decreased side effects.     

Dehydro-dermorphins

Dehydrophenylalanine having the Z-configuration (ΔPhe) and D-Phe were incorporated in positions 3 and/or 5 into dermorphin-(1–5)-peptide amide (H-Tyr-D-Ala-Phe-Gly-Tyr-NH₂) in order to study the effect of structure or configurational changes. On GPI preparation, whereas the activity of [L-Phe⁵]-pentapeptide was fourfold higher than parent peptide and comparable to that of dermorphin, the substitution of Phe³ by its D-enantiomer was barely tolerated. The pentapeptides containing ΔPhe in positions 3 and/or 5 displayed even lower potency: particularly the unsaturation at position 3 alone or at position 3 and 5 was very detrimental to μ activity.     

The use of opioids in neonates. A retrospective study of 933 cases

This is a retrospective study on the use of postoperative opioids in neonates admitted to the surgical intensive care unit at Great Ormond Street over a 5-year period (1980-84). A total of 131 (14%) babies received opioids out of 933 neonates admitted to the unit. The use of opioids increased from 9.7% to 27.2% of admitted cases during the survey period. Postoperative ventilation of the lungs was necessary in 240 (25.7%) cases and 88 (36.6%) of these were given opioids. Four babies initially failed to wean from controlled ventilation as a result of opioid induced respiratory depression. A total of 51 (7.35%) spontaneously breathing neonates received opioids and seven (13.7%) of these developed apnoea or respiratory failure thought to be induced by opioids. The administration of opioids by nurses occurred most frequently in the late evening and early hours of the morning, when medical cover is at its lowest level.     

Opioid peptides Synthesis and binding properties of dermorphin related heptapeptides

C-Terminal amino acid residues of dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH₂) were replaced by N^α-methyl- or D-amino acids in order to examine the effect on opioid activity. In binding studies based on displacement of μ, Δ, and κ opioid receptor selective radiolabels from guinea pig brain membranes, the 13 new analogues showed, like dermorphin, a negligible affinity for the κ binding site. The introduction of N^α-methyl- or D-amino acid residues at position 5, 6, or 7 of dermorphin, when matched with C-terminal amide function modifications, generally produced analogues with reversed μ/δ specificity.