Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00345 (ICI)
 5,388 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Propofol (2,6-diisopropylphenol, Diprivan, ICI-Pharmaceuticals, Manchester, UK) is widely used either as an adjunct in general anaesthesia or as sole anaesthetic agent by the continuous intravenous route and intermittent bolus injections for minor surgical interventions. For several years, we have been using this kind of anaesthesia in transvaginal oocyte retrieval for in-vitro fertilization (IVF), allowing a completely painless puncture on an out-patient basis. From in-vitro studies on mouse oocytes, it appeared that propofol could be deleterious for fertilization in a dose- and time-dependent manner. We therefore investigated the concentrations of propofol in follicular fluid during oocyte retrieval in women. We measured propofol levels in serum and follicular fluid of nine patients at fixed intervals during ultrasound guided oocyte retrieval. Serum levels fluctuated randomly, due to interference from top-off doses of propofol. In follicular fluid, however, we found a steady increase of propofol levels, which was proportional to the total dose of propofol administered. These data indicate that propofol accumulates in follicular fluid. Although it seems unlikely that propofol as used in the present protocol exerts a clinically significant unfavourable effect on IVF, we suggest that the oocyte retrieval procedure should be kept as short as possible, in order to limit the accumulation of the anaesthetic in follicular fluid.
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PMID:Propofol anaesthesia for ultrasound guided oocyte retrieval: accumulation of the anaesthetic agent in follicular fluid. 129 69

Hypogonadal (hpg) mutant mice, with a congenital deficiency of hypothalamic gonadotrophin-releasing hormone (GnRH), and testicular feminized (tfm) mice, which lack a functional androgen receptor, were used to study the effects of the potent GnRH agonist 'Zoladex' (ICI 118630; D-Ser (Bu(t))6, Azgly10-GnRH) on pituitary and gonadal function. Zoladex (0.5 mg) in a sustained-release lactide-glycolide copolymer depot was administered subcutaneously under anaesthesia and was left in place for 7 days, after which time the effects of the drug upon pituitary and serum gonadotrophin concentrations, glycoprotein hormone subunit mRNAs and testicular morphology were investigated. At the pituitary level, Zoladex treatment resulted in a substantial reduction in LH content in normal males, and LH content was depressed in hpg mice even below the basal levels normally found in these mutants. Pituitary LH content in the Zoladex-treated animals was depressed in the tfm groups, but not to the same levels as those found in the normal and castrated normal mice. Zoladex treatment at the time of castration prevented the post-operative elevation in serum LH associated with castration alone. In the androgen-deficient tfm mouse, Zoladex did not depress the normally elevated serum LH levels. Serum LH in the hpg animals was, in all cases, below the limit of detection of the assay. Pituitary FSH content was depressed into the hpg range in both the normal and castrated animals, but there was no further depression in the hpg mice. The pituitary content was reduced in the tfm mice, again the effects not being as dramatic as in the normal and castrated animals. Serum FSH content, as measured by radioimmunoassay, was depressed by 50% in normal mice; there was no reduction in the hpg mice, however. With regard to pituitary gonadotrophic hormone gene expression, Zoladex administration to normal mice caused a dramatic reduction in LH beta mRNA content, to a level approximating that found in untreated hpg mice. The drug also depressed LH beta mRNA in the castrated group to the hpg range when given at the time of castration, whereas in untreated castrated mice there was a significant increase in LH beta mRNA. In the tfm mouse, which can be considered as a model for long-term failure of androgen feedback, Zoladex again induced a fall in LH beta mRNA, but not to the same extent as in the normal and normal castrated group. Zoladex had no effect on the already low levels of LH beta mRNA found in hpg mice.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of the gonadotrophin-releasing hormone agonist 'Zoladex' upon pituitary and gonadal function in hypogonadal (hpg) male mice: a comparison with normal male and testicular feminized (tfm) mice. 138 60

We investigated alterations in myocardial beta- and beta 1-adrenergic receptor (BAR and B1AR) number during hyperdynamic state induced by endotoxin or cytokines. [METHODS] Twenty-nine Japanese White rabbits were divided into 2 groups. Hearts were removed 18 h after intraperitoneal administration of sterile saline (SAL) or E. coli endotoxin (LPS; 50 micrograms/kg) (Group E, n = 12), or 3 h after intravenous injection of SAL or cytokines (interleukin 1-beta; 5 micrograms/kg followed by 25 ng/kg/min for 2 h, or tumor necrosis factor; 5 micrograms/kg) (Group C, n = 17). BAR and B1AR numbers were determined in myocardial membranes from rabbit left ventricles with techniques of radioactive ligand binding study. We used [3H] dihydroalprenolol (3H-DHA) as radioactive ligand, and specific 3H-DHA binding to BARs was defined as the difference between the presence and the absence of 10 microM propranolol. B1AR number was assessed through the specific binding of 3H-DHA in the presence of ICI 118, 551 (5 x 10(-8) M), a highly selective beta 2-adrenergic receptor antagonist. In Group E, mean arterial blood pressure (MAP), heart rate (HR), and cardiac output (CO) (by thermodilution) were measured under pentobarbital sodium anesthesia before excision of hearts. [RESULTS] In Group E, CO was significantly (p less than 0.05) increased in rabbits injected with LPS (E-LPS) as compared with that in rabbits injected with SAL (E-SAL) (E-LPS; 0.75 +/- 0.02 l.min-1, E-SAL; 0.61 +/- 0.05 l.min-1, mean +/- SEM). MAP and HR were slightly decreased in E-LPS but not significantly. Maximum binding (Bmax) of 3H-DHA to BARs was significantly (p less than 0.05) decreased by 18% in myocardial membranes from E-LPS compared to E-SAL (E-LPS; 48.2 +/- 4.3 fmol/mg protein, E-SAL; 58.9 +/- 2.9 fmol/mg protein, mean +/- SEM). Similarly, Bmax of 3H-DHA to B1ARs was decreased by 18% in E-LPS, although no statistical significance was detected. In Group C, both BAR and B1 AR number was slightly, but not significantly decreased 3 h after administration of cytokines. [CONCLUSION] These data suggest that down regulation of cardiac BARs may occur during hyperdynamic stage of endotoxic shock.
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PMID:[Alterations in number of rabbit myocardial beta-adrenergic receptors in endotoxic shock: down regulation in hyperdynamic sepsis model and effects of cytokines administration]. 166 39

The authors investigated the comparative roles of beta 1- and beta 2-adrenoceptors in myocardial sensitization by halothane in dogs. The arrhythmogenic dose (AD) of isoproterenol was determined in the presence of various doses of phenylephrine during halothane anesthesia in dogs, and the influences of 1-metoprolol (beta 1-antagonist) and ICI-118,551 (beta 2-antagonist) on the AD were examined. In the presence of 1-metoprolol, the AD of isoproterenol was significantly greater than the control, but in the presence of ICI-118,551, the AD of isoproterenol was lower. Blood pressure during the arrhythmias was higher in the presence of ICI-118,551 than that in controls. In addition, the AD of ritodrine (beta 2-agonist) was also determined at various doses of phenylephrine. The interaction between phenylephrine and ritodrine in inducing arrhythmias showed hyperbolic isoboles. However, 1-metoprolol completely inhibited the occurrence of arrhythmias induced by ritodrine and phenylephrine. The results suggest that myocardial beta 1-adrenoceptors play an essential role in the genesis of arrhythmias during halothane anesthesia in dogs, whereas beta 2-adrenoceptors do not.
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PMID:Roles of beta 1- and beta 2-adrenoceptors in the mechanism of halothane myocardial sensitization in dogs. 167 87

1. We studied the effect of bradykinin on plasma exudation in the airways of the anaesthetized guinea-pig in vivo. Tissue content of extravasated Evans blue dye was used as an index of protein exudation in the larynx, trachea, main bronchi and intrapulmonary airways (i.p.a.). 2. Bradykinin increased the content of Evans blue in all tissues studied in a dose-related manner. The response was greatest in the main bronchi and i.p.a., less in the trachea and least in the larynx. A dose of 47 nmol kg-1 was the lowest tested which caused significant (P less than 0.001) plasma exudation with increases in leakage above control values of 256% in the larynx, 405% in the trachea, 394% in the main bronchi and 485% in intrapulmonary airways. 3. Leakage was significantly (P less than 0.05) increased above control values by 1 min after bradykinin (47 nmol kg-1) in the main bronchi and intrapulmonary airways and was maximal in all airways 5 min after bradykinin. Although reduced by 15 min, the tissue content of dye was still significantly (P less than 0.05) increased 2 h after bradykinin. 4. The prolonged tissue dye retention was due to a later phase of slow and maintained exudation preventing full clearance of dye after the initial response. 5. The initial phase of leakage was partially attenuated by the platelet activating factor (PAF) receptor antagonists WEB 2086 or BN 52021, by indomethacin or by inhibiting sensory nerve activation by opioid anaesthesia: it was not affected by mepyramine and cimetidine nor by the sulphidopeptide leukotriene receptor antagonists FPL 55712 or ICI 198,615. Adrenoceptor blockade of the anti-leakage effects of endogenously-released catecholamines significantly (P < 0.05) enhanced leakage. 6. The later phase of plasma leakage was completely inhibited by the PAF antagonists. 7. We conclude that, in guinea-pig airways in vivo, the initial phase of bradykinin-induced plasma exudation is mediated in part by PAF, sensory nerves and prostaglandins, whereas the later, prolonged phase of leakage is mediated exclusively by PAF. If bradykinin is generated in asthma, its potent and prolonged effects on plasma leakage may contribute significantly to airway oedema and may be involved in the development of bronchial hyperresponsiveness.
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PMID:Bradykinin-induced plasma exudation in guinea-pig airways: involvement of platelet activating factor. 207 90

The importance of the interaction of alpha- and beta-adrenoceptors in maintaining vascular tone in rats was studied. This interaction after clenbuterol (CLEN) treatment indicates an important contribution of the circulating epinephrine (EPI) levels. In urethane-anesthetized rats, the beta 2-adrenoceptor antagonist ICI 118.551 was more effective in antagonizing isoproterenol-induced hypotension (mainly beta 2-mediated) than tachycardia (mainly beta 1-mediated). Intravenous (i.v.) administration of the alpha 2-adrenoceptor agonist clonidine (CLO) induced an initial pressor response followed by a more prolonged hypotension and bradycardia. The initial hypertensive effect was potentiated by previous acute administration of ICI 118.551 as well as by the nonselective beta-adrenoceptor antagonist propranolol, but not by metoprolol, a more selective beta 1-blocker. Fourteen days of administration of the beta 2-adrenoceptor agonist CLEN [0.3 mg/kg, subcutaneously (s.c.) twice daily], a treatment that induces desensitization of beta 2-mediated vasodilation, increased the pressor response induced by CLO, an effect that was not observed in pentobarbital-anesthetized rats. In any case, neither beta-blockers nor CLEN treatment affects the hypotension and bradycardia induced by CLO. Mean blood pressure (BP) of CLEN-treated rats was increased under urethane anesthesia but not under pentobarbital anesthesia. Catecholamine levels (principally EPI) were higher in urethane-anesthetized rats. These results provide further evidence of a functional interaction between alpha 2- and beta 2-adrenoceptor-mediated responses in rat vasculature and suggest that vasodilator beta 2-adrenoceptors might contribute to the determination of peripheral vascular tone when circulating EPI is substantially elevated.
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PMID:Further evidence of interaction between vasodilator beta 2- and vasoconstrictor alpha 2-adrenoceptor-mediated responses in maintaining vascular tone in anesthetized rats. 248 76

Opioid substances have been shown to stimulate and depress the secretion of ACTH in the rat. Their opposing actions appear to be mediated in part by specific receptors in the hypothalamus which influence the secretion of corticotrophin-releasing factor (CRF). In an attempt to determine the physiological role of these receptor systems, experiments were carried out in which the plasma ACTH and serum corticosterone concentrations were determined before and after stress in rats treated s.c. with selective antagonists of mu-(naloxone, naltrexone), delta-(ICI 174864) and kappa-(MR2266) opioid receptors. Neither naloxone (25-100 micrograms/100 g) nor naltrexone (50 micrograms/100 g) influenced the resting plasma ACTH or serum corticosterone concentrations. However, both inhibited (P less than 0.01) the secretion of the two hormones elicited normally by surgical stress (laparotomy under ether anaesthesia). ICI 174864 (30-100 micrograms/100 g) also had little effect on resting hypothalamo-pituitary-adrenocortical (HPA) activity but, at the highest dose, it caused a small (P less than 0.05) potentiation of the response to surgery. In contrast, MR2266 (150-300 micrograms/100 g) produced marked activation of the HPA system and not only stimulated the resting secretion of ACTH and corticosterone but also potentiated and prolonged the HPA response to stress. The results suggest that mu- and kappa-opioid receptors mediate opposing actions of endogenous opioid peptides, both of which may be physiologically important in the regulation of CRF release.
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PMID:Effects of selective opioid-receptor blockade on the hypothalamo-pituitary-adrenocortical responses to surgical trauma in the rat. 254 2

Propofol, 2-6 diisopropylphenol ("Diprivan", ICI) has been shown to be safe and effective for induction and maintenance of anesthesia when injected intravenously. Its pharmacological profile suggests that it may prove to be a useful agent in obstetric anesthetic practice. But, obstetrics is a specialized field in which the acute effects of the anesthetic agent on the fetus must be considered. This open non comparative study was therefore designed to investigate the neonatal assessments when propofol was used either for induction of anesthesia or for induction and maintenance of anesthesia during elective cesarean section. This study was conducted in two separate phases according to the use of propofol. In both phases, anesthesia was induced with an intravenous bolus of 2.5 mg.kg-1 of propofol. In phase 1 (n = 10), anesthesia was maintained with 50% nitrous oxide in oxygen and halothane. In phase 2 (n = 11), a continuous infusion of propofol at a rate of 5 mg.kg-1.h-1 was started after the induction dose. At time of delivery, blood samples were taken from maternal artery, umbilical vein and artery for acid-base and blood gas status. The condition of the infant was evaluated using Apgar score at 1, 5 and 10 min, time to sustained spontaneous respiration and the Neurologic and Adaptative Capacity Score was assessed at 30 min, 2 hours and 24 hours after birth. Maternal and neonatal blood gas tensions and acid-base status at delivery were within the normal clinical limits in both phases and compared favorably with results published by others workers using established methods of anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Neonatal effects of propofol administered to the mother in anesthesia in cesarean section]. 260 37

To discover why trabeculectomy often fails in children, we studied a series of 27 procedures, focusing on intraocular and scleral factors that prevent humoral drainage. Gonioscopy was performed under anesthesia with Fluothan (ICI, UK), and trabeculectomy was considered successful when values were equal to or lower than 20 mm Hg. Only ten procedures proved successful, and all had large basal iridectomies plus visible anterior scleral openings at gonioscopy. Possible causes for the 17 failures are listed, together with indications for revision surgery.
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PMID:Gonioscopic findings in trabeculectomies in young children. 272 75

Intraventricular infusions of adrenaline and various pharmacological agents acting on beta-adrenergic receptor subtypes were carried out in rats orchidectomized 16 h previously. Infusions (10 microliter) of solutions containing the drugs were administered under anaesthesia induced with alphaxalone and alphadolone. Levels of LH were measured in plasma collected immediately before and at predetermined intervals after the infusion. The acute rise in LH levels after castration was increased still further by isoprenaline (a mixed beta 1- and beta 2-agonist), fenoterol (a beta 2-agonist) and atenolol (a beta 1-antagonist). In contrast, prenalterol (a beta 1-agonist) and (2RS,3RS)-3-isopropylamino-1-(7-methylindan-4-yloxy)++ +butan-2-ol (ICI 118,551) (a selective beta 2-antagonist) were inhibitory to LH release. Adrenaline itself, salbutamol (another selective beta 2-agonist), propranolol (a mixed beta-antagonist) and metoprolol (a beta 1-antagonist) did not significantly alter plasma LH concentrations at the doses administered. The stimulatory effect of isoprenaline on LH release was partially reduced when given together with ICI 118,551, but was not affected when administered simultaneously with atenolol. The inhibitory effect of ICI 118,551 was, however, prevented by concomitant administration with fenoterol, as was that of prenalterol when infused with atenolol. The results suggest that the hypothalamic mediation of the short-term changes in LH release in response to castration is exerted, at least in part, through the activation of a beta 2-stimulatory component and the suppression of a beta 1-inhibitory component.
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PMID:The role of the hypothalamic beta-adrenergic system in controlling the LH rise in short-term castrated rats. 288 30


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