Serotonin toxicity caused by an interaction between fentanyl and paroxetine

PURPOSE: To report a case of serotonin toxicity, presenting in the postoperative period, caused by an interaction between paroxetine (a selective serotonin reuptake inhibitor, SSRI) and fentanyl (a phenylpiperidine opioid). Serotonin toxicity precipitated by fentanyl is unusual and has not previously been described in combination with SSRIs in the perioperative setting. CLINICAL FEATURES: A 60-yr-old woman, established on paroxetine for depression, underwent excision of a chest wall myxofibrosarcoma and chest wall reconstruction. Fentanyl was administered for intraoperative and postoperative analgesia (1 mg intraoperatively, and 2.5 mg by infusion in the first 36 hr, postoperatively). She developed a vague affectation, intermittent agitation, bilateral hyper-reflexia, inducible clonus, and a period of hypertension, suggestive of serotonin toxicity. There was complete resolution after cessation of fentanyl and paroxetine.Conclusion: The co-administration of SSRIs and fentanyl may precipitate serotonin toxicity. There must be consideration of this unusual interaction when administering fentanyl to patients established on SSRIs. Physicians should be vigilant of the features of serotonin toxicity developing in such patients.     

人参叶中微量新皂甙-La的分离与鉴定

前已报道从人参(Panax ginseng C.A.Meyer)叶中分到三种微量新皂甙。在继续研究的基础上,又得到一个微量新皂甙,命名为人参皂甙-La(ginsenoside-La)。人参皂甙-La,无色针晶(MeOH),[α]D~(20)—18.4(Pyridine-d_5)。负离子FAB-MS     

The action of ganglionic blocking drugs on the synaptic responses of rat submandibular ganglion cells

1 The effects of tubocurarine, hexamethonium and trimetaphan on the synaptic currents of rat submandibular ganglion cells have been measured at 20°C by means of a two-microelectrode voltage-clamp system. The aim was to distinguish between the receptor-blocking and channel-blocking actions of those drugs, and to test for possible selectivity of action on the `fast' and `slow' acetylcholine-operated channels.     

Depolarization of nonmyelinated fibers of the rat vagus nerve produced by activation of protein kinase C

The effect of activation of protein kinase C by phorbol esters has been studied on the nonmyelinated (C) fibers of the rat vagus nerve. Grease-gap recording at room temperature was used to monitor changes in the resting and action potentials. Effects of phorbol esters on the rate of efflux of 86Rb and 14C-guanidinium were also measured. The active isomer beta-phorbol 12,13-dibutyrate (PDBu), applied for 10 min at concentrations of 10 nM to 3 microM, caused a slowly developing depolarization, which persisted after the drug was washed out. The action potential was concomitantly reduced. These effects did not occur with the inactive isomer alpha-phorbol 12,13-didecanoate. The PDBu-induced depolarization was reduced by about 75% if Na+ was replaced by the impermeant cation N-methyl-(+)-glucamine (NMG); the residual effect was almost abolished if the nerves were presoaked in a solution containing gluconate in place of Cl-. It was concluded that increases in conductance mainly to Na+ and Cl- were responsible for the depolarization. The response was unaffected by tetrodotoxin or calcium-channel blockers. Omission of Ca2+, surprisingly, enhanced the PDBu-induced depolarization 3-5-fold; furthermore, addition of 2 mM Ca2+ following a PDBu-induced depolarization recorded in Ca2+-free solution caused a pronounced repolarization. This effect of Ca2+ occurred also with Sr2+ and Ba2+, but not with other divalent cations or with La3+. Divalent cations known to block Ca channels inhibited the repolarizing action of Ca2+. These results suggested that Ca2+ acts intracellularly, either to block Na channels opened by PDBu or to activate protein phosphatases. The PDBu-induced response in Ca2+-free solution was increased 2-fold by a reduction in pH from 7.4 to 6.5. Under normal conditions the nerve was reversibly depolarized by this pH change; after PDBu this pH sensitivity was enhanced, and depolarization occurred at a less acidic pH. PDBu caused a 3-4-fold increase in the rate of efflux of 86Rb (a marker for K+ ions) and of 14C-guanidinium (a marker for Na+ ions) from preloaded nerves. These effects, in contrast to the depolarization, were transient.(ABSTRACT TRUNCATED AT 400 WORDS)     

甘草叶中甘草宁P-3′-甲醚的分离和鉴定

Two flavonoids were isolated from the leaves of Glycyrrhiza uralensis Fisch (Licorice, Leguminosae). On the basis of physico-chemical properties and spectroscopy (UV, ¹HNMR and MS), a new compound was elucidated as 3,5,7,4′-tetrahydroxy-3′-methoxy- 6-isoprenyl flavone (gancaonin P-3′-methylether) and another known compound was identified as 8-C-prenyleriodictyol.     

2,4-二氨基-5-取代苄基嘧啶类化合物的合成及其抑酶活性

本文设计并合成了18个在苄基上带有不同体积取代基的2,4-二氨基-5-取代苄基嘧啶类化合物。测定了这些化合物对乳酪菌二氢叶酸还原酶及对鸡肝二氢叶酸还原酶的表观50%抑制作用。其中2,4-二氨基-5-(3′-羟基-4′-甲氧基)苄基、2,4-二氨基-5-(3′-甲氧基-4′-甲氧乙氧基)苄基嘧啶对上述二氢叶酸还原酶(DHFR)的选择性较好。     

An analysis of the action of a false transmitter at the neuromuscular junction.

1. The action of monoethylcholine (MECh) on neuromuscular transmission has been studied by electrophysiological methods. 2. End-plate potentials (e.p.p.s.) in curarized rat muscle were unaffected or slightly increased in amplitude by MECh (0-1-1 mM). Stimulation at 3 Hz for about 30 min in the presence of MECh caused a progressive decline in e.p.p. amplitude, and a shortening of the e.p.p. time course. These changes were reversed by addition of choline to the medium. Similar changes in amplitude, but no change in time course, occurred when the preparation was stimulated in the presence of hemicholinium or triethylcholine. 3. Extracellular recordings of miniature end-plate potentials in frog muscle showed that stimulation in the presence of MECh caused the time constant of the exponential decay of the m.e.p.p.s. to decrease by 42%. The amplitude of intracellular m.e.p.p.s. was reduced by 45%. These changes were maximal by the time about 3 X 10(5) quanta had been released. 4. Voltage clamp experiments in rat muscle in which miniature end-plate currents (m.e.p.c.s) were recorded showed that stimulation in the presence of MECh reduced the amplitude (by 33%) and the decay time constant (by 42%). 5. Analysis of end-plate current flucutations produced by local application of acetylcholine (ACh) and acetylmonoethycholine (AMECh) to voltage clamped rat end-plates showed that the amplitude of the elementary current events was the same for both compounds whereas the average channel lifetime was 44% shorter for AMECh than for ACh. 6. The voltage-sensitivity of the channel lifetime (measured from end-plate current fluctuations) was the same for ACh and AMECh. The voltage-sensitivity of the m.e.p.c. decay time constant was the same as that found from noise measurements. The shortened m.e.p.c.s. (false m.e.p.c.s.) occurring after stimulation in the presence of MECh also showed the same voltage-sensitivity. 7. Both normal and false m.e.p.c.s. were prolonged by neostigmine by almost the same factor; false m.e.p.c.s. were thus shorter than normal m.e.p.c.s. even when cholinesterase was inactivated. Experiments with progressive curarization of neostigmine-treated end-plates suggested that the fraction of transmitter molecules bound is smaller for false than for normal m.e.p.c.s. The difference implies that the false transmitter has one quarter of the affinity of ACh for the receptors. 8. It is concluded that stimulation in the presence of MECh gives rise to a false transmitter, presumably AMECh, which has a lower affinity for receptors than ACh, and gives rise to ionic channels with a shorter average lifetime than those activated by ACh.