ABSTRACT
The mechanism underlying the relaxant response of rat aortic rings to the diterpene jatrophone was investigated. Jatrophone (3 and 10 microM) did not affect acetylcholine-induced endothelium-dependent relaxations, but caused concentration-dependent inhibition of noradrenaline (NA)-induced concentrations in unrubbed, and to a lesser extent, in denuded rings. Jatrophone (30 microM) fully prevented responses to angiotensin II and NA, while responses to KCl (up to 220 mM) were unaffected. In depolarizing medium (KCl 40 mM), jatrophone (3-30 microM) antagonized Ca(2+)-induced contractions in a concentration-dependent and noncompetitive manner, while verapamil (10-100 nM) caused a concentration-dependent, rightward displacement and depression of the Ca2+ concentration-response curve. Jatrophone (1 to 300 microM) concentration dependently relaxed rat aortic rings precontraction with either NA (1 microM) or KCl (80 mM), yielding EC50 s of 11 and 24 microM, respectively. These relaxant responses to jatrophone were unaffected by glibenclamide (1 microM), but the concentration-response curve was displaced to the right (2- to 8-fold) by other K+ channel blockers such as tetraethylammonium (10 and 30 mM), 4-aminopyridine (3 and 10 mM) or procaine (1 and 3 mM). These results indicate that jatrophone relaxes the rat aorta, at least in part, by activating K+ channels distinct from the ATP-sensitive subtype. Since jatrophone, like verapamil, relaxed preparations contracted with KCl and inhibited Ca(2+)-induced contractions in depolarized preparations, this diterpene may also block Ca2+ influx through voltage-sensitive channels. However, additional actions of jatrophone on receptor-operated Ca2+ channels causing Ca2+ efflux and/or release cannot be fully ruled out.
Subject(s)
Aorta, Thoracic/drug effects , Diterpenes/pharmacology , Muscle, Smooth, Vascular/drug effects , Potassium Channels/drug effects , Animals , Aorta, Thoracic/physiology , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiology , In Vitro Techniques , Male , Muscle Contraction/drug effects , Muscle Relaxation/drug effects , Muscle Relaxation/physiology , Muscle, Smooth, Vascular/physiology , Norepinephrine/pharmacology , Potassium Chloride/pharmacology , Rats , Rats, Inbred StrainsABSTRACT
As primeiras tentativas de avaliar o bloqueio neuromuscular residual em seres humanos foram baseadas na observaçäo de sinais clínicos, e na verificaçäo de parâmetros respiratórios como volume-minuto, capacidade vital e força inspiratória máxima. No entanto, o melhor método para monitorizar a transmissäo neuromuscular é a estimulaçäo de um nervo motor periférico e a mensuraçäo da resposta evocada no músculo por ele inervado. As principais características de um estimulador de nervo periférico, tais como freqüência, duraçäo e forma do pulso, voltagem e intensidade da corrente, bem como as características de conexäo entre o paciente e o estimulador como o tipo de polaridade do eletrodo, e o local de sua colocaçäo no paciente säo revistos. Säo discutidas as informaçöes que podem ser obtidas pela estimulaçäo do nervo ulnar ou eventualmente por outro nervo periférico, de modo visual ou táctil, ou através de registros eletromecânicos ou de eletromiografia. As interpretaçöes clínicas dessas informaçöes säo também analisadas
Subject(s)
Humans , Electromyography , Monitoring, Physiologic , Neuromuscular Junction , Ulnar NerveABSTRACT
The antiemetic effect of clebopride, a new derivative of the orthopramide group, was compared with that of placebo in 298 women undergoing elective surgery. A group of 150 patients received premedication of 1 mg/kg of meperidine, administered intramuscularly (IM), and a group of 148 patients received premedication of 10 mg of diazepam IM. All patients received 0.5 mg of atropine IM. Anesthesia was induced with thiopental and maintained with halogenated N2O/O2. In a double-blind procedure, clebopride (2 mg) or placebo was injected IM at the end of anesthesia and whenever a patient had a second episode of vomiting. Clebopride appeared to be better than placebo in the prevention of nausea (P less than or equal to 0.05) and vomiting (P less than or equal to 0.001) during the 12-hour observation period. The frequency of side effects was virtually the same in patients given clebopride and patients given placebo.
Subject(s)
Antiemetics/therapeutic use , Benzamides/therapeutic use , Nausea/prevention & control , Vomiting/prevention & control , Adolescent , Adult , Antiemetics/administration & dosage , Benzamides/administration & dosage , Female , Humans , Injections, Intramuscular , Middle Aged , Postoperative Complications/prevention & control , Preanesthetic MedicationABSTRACT
The inhibitory effect of ketamine on the agonist-induced contraction of isolated rat uteri was compared with that of papaverine and verapamil. Under similar experimental conditions papaverine and verapamil were found to be more potent than ketamine. When preparations were preincubated for 20 min with either ketamine (3 X 10(-5) to 10(-3) M) or papaverine (10(-6) to 10(-5) M), a noncompetitive antagonism was observed against oxytocin with pD'2 values of 3.67 +/- 0.07 and 5.13 +/- 0.10, respectively. A noncompetitive form of antagonism was also observed by papaverine against BaCl2 with pD'2 values of 4.59 +/- 0.15, while ketamine produced competitive antagonism with a pA2 value of 4.68 +/- 0.12. It was also demonstrated that all three inhibitory drugs interfere competitively with Ca2+ on the rat uteri. However, ketamine was shown to be less potent than verapamil and papaverine in antagonizing the effects owing to an increased Ca2+ concentration in the medium. These results are consistent with previous publications that ketamine has a papaverinelike effect on the rat uteri and suggest that the relaxation promoted in this preparation is due, at least in part, to blockade of the Ca2+ translocation processes.
