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Agonist Used (agonist + used)
Selected AbstractsEffects of long-term exposure to ramelteon, a melatonin receptor agonist, on endocrine function in adults with chronic insomniaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 2 2009Gary Richardson Abstract Objective To evaluate the effects of ramelteon, an MT1/MT2 melatonin receptor agonist used to treat insomnia, on endocrine function in adults with chronic insomnia. Methods This was a double-blind, placebo-controlled, trial of adults (18,45 years) with chronic insomnia. Subjects received either ramelteon 16,mg or placebo nightly for 6 months. Hormonal measures of the thyroid, reproductive, and adrenal axes were analyzed monthly and compared with baseline and placebo values. Results While isolated changes were detected at some time points, there were no consistent statistically significant differences between treatments on measures of thyroid function (total T4, free T4, TSH, and total T3), adrenal function (AM cortisol, and ACTH), or on most reproductive endocrine measures [LH, FSH, estradiol (women), total, and free testosterone (men)]. Prolactin concentrations were increased overall in women in the ramelteon group compared with placebo (p,=,0.003). No clinical effects of elevated prolactin were reported; average menstrual cycle length, duration of menses, and ovulation probability did not differ between groups. Conclusions Long-term exposure to ramelteon 16,mg, a potent melatonin receptor agonist, resulted in mild, transient increase in prolactin, in women only, that were not associated with measurable reproductive effects. There were no consistent changes in other endocrine measures. Copyright © 2008 John Wiley & Sons, Ltd. [source] Tocolytic Effects of a Long-acting ,2 -Adrenoceptor Agonist, Formoterol, in RatsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2000NORIHIRO SHINKAI We have assessed the tocolytic activity of formoterol, a novel long-acting and potent ,2 -adrenoceptor agonist, through its production of cyclic adenosine monophosphate, in comparison with ritodrine, a ,2 -adrenoceptor agonist used clinically to counter premature delivery. Formoterol and ritodrine inhibited the amplitude and frequency of rat uterine contraction, with IC50 values of 3.8 times 10,10 and 4.7 times 10,7 M, respectively. Intravenous administration of formoterol or ritodrine caused inhibition of uterine motility and increased heart rate in a dose-dependent manner. Inhibition of uterine motility by oral administration of formoterol (0.3 and 1 mg kg,1) continued for at least 60 min, whereas that with ritodrine (100 mg kg,1) persisted for 15 min with rapid recovery thereafter in pregnant rats. The ,-adrenoceptor binding of [125I]iodopindolol to the myometrium of pregnant rats was competitive with formoterol and ritodrine, with Ki values of 0.04 and 6.10 nM, respectively. Formoterol (10,6 , 10,4 M) and ritodrine (10,6 , 10,4 M) increased the level of cyclic adenosine monophosphate in lymphocytes in a dose-dependent manner. The results suggested that formoterol caused relaxation of uterine motility through production of cyclic adenosine monophosphate. Thus, formoterol may be useful as a treatment to counter premature delivery. [source] Quantification of clenbuterol in equine plasma, urine and tissue by liquid chromatography coupled on-line with quadrupole time-of-flight mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 17 2002Fuyu Guan Clenbuterol (CBL) is a potent ,2 -adrenoceptor agonist used for the management of respiratory disorders in the horse. The detection and quantification of CBL can pose a problem due to its potency, the relatively low dose administered to the horse, its slow clearance and low plasma concentrations. Thus, a sensitive method for the quantification and confirmation of CBL in racehorses is required to study its distribution and elimination. A sensitive and fast method was developed for quantification and confirmation of the presence of CBL in equine plasma, urine and tissue samples. The method involved liquid-liquid extraction (LLE), separation by liquid chromatography (LC) on a short cyano column, and pseudo multiple reaction monitoring (pseudo-MRM) by electrospray ionization quadrupole time-of-flight tandem mass spectrometry (ESI-QTOF-MS/MS). At very low concentrations (picograms of CBL/mL), LLE produced better extraction efficiency and calibration curves than solid-phase extraction (SPE). The operating parameters for electrospray QTOF and yield of the product ion in MRM were optimized to enhance sensitivity for the detection and quantification of CBL. The quantification range of the method was 0.013,10,ng of CBL/mL plasma, 0.05,20,ng/0.1,mL of urine, and 0.025,10,ng/g tissue. The detection limit of the method was 13,pg/mL of plasma, 50,pg/0.1,mL of urine, and 25,pg/g of tissue. The method was successfully applied to the analysis of CBL in plasma, urine and various tissue samples, and in pharmacokinetic (PK) studies of CBL in the horse. CBL was quantified for 96,h in plasma and 288,h in urine post-administration of CLB (1.6,µg/kg, 2,×,daily,×,7 days). This method is useful for the detection and quantification of very low concentrations of CBL in urine, plasma and tissue samples. Copyright © 2002 John Wiley & Sons, Ltd. [source] Gq/11 and Gi/o activation profiles in CHO cells expressing human muscarinic acetylcholine receptors: dependence on agonist as well as receptor-subtypeBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2001Elizabeth C Akam Profiles of G protein activation have been assessed using a [35S]-GTP,S binding/immunoprecipitation strategy in Chinese hamster ovary cells expressing either M1, M2, M3 or M4 muscarinic acetylcholine (mACh) receptor subtypes, where expression levels of M1 and M3, or M2 and M4 receptors were approximately equal. Maximal [35S]-GTP,S binding to Gq/11, stimulated by M1/M3 receptors, or Gi1 , 3, stimulated by M2/M4 receptors occurred within approximately 2 min of agonist addition. The increases in Gq/11,-[35S]-GTP,S binding after M1 and M3 receptor stimulation differed substantially, with M1 receptors causing a 2 , 3 fold greater increase in [35S]-GTP,S binding and requiring 5 fold lower concentrations of methacholine to stimulate a half-maximal response. Comparison of M2 and M4 receptor-mediated Gi1 , 3,-[35S]-GTP,S binding also revealed differences, with M2 receptors causing a greater increase in Gi1 , 3, activation and requiring 10 fold lower concentrations of methacholine to stimulate a half-maximal response. Comparison of methacholine- and pilocarpine-mediated effects revealed that the latter partial agonist is more effective in activating Gi3, compared to Gi1/2, for both M2 and M4 receptors. More marked agonist/partial agonist differences were observed with respect to M1/M3 -mediated stimulations of Gq/11,- and Gi1 , 3,-[35S]-GTP,S binding. Whereas coupling to these G, subclasses decreased proportionately for M1 receptor stimulation by these agonists, pilocarpine possesses a greater intrinsic activity at M3 receptors for Gi, versus Gq/11, activation. These data demonstrate that mACh receptor subtype and the nature of the agonist used govern the repertoire of G proteins activated. They also provide insights into how the diversity of coupling can be pharmacologically exploited, and provide a basis for a better understanding of how multiple receptor subtypes can be differentially regulated. British Journal of Pharmacology (2001) 132, 950,958; doi:10.1038/sj.bjp.0703892 [source] Pregnancy outcomes following cabergoline treatment: extended results from a 12-year observational studyCLINICAL ENDOCRINOLOGY, Issue 1 2008Annamaria Colao Summary Objective, Cabergoline is a dopamine agonist used to treat hyperprolactinaemia. Because hyperprolactinaemia is a significant cause of infertility in women, cabergoline and other dopamine agonists are frequently prescribed to reduce prolactin levels and restore normal menses. They are usually discontinued shortly after the patient becomes pregnant. Although cabergoline has been used to treat hyperprolactinaemia since the mid-1990s, safety data related to maternal and foetal exposure to this agent are still limited. Design, The current prospective, observational study reports on a total of 380 pregnancies. This extends by 154 pregnancies the results of a previously published interim report on the outcomes of 226 pregnancies in women treated with cabergoline up to 1994. Main outcome measures, Outcomes examined include the incidence of abortions and premature delivery and the number and types of foetal malformations or abnormalities. Results, Follow-up data were available for 329 pregnancies, including 258 (78%) deliveries and 71 (22%) abortions. Of the 71 reported abortions, 31 (44%) were voluntary, 30 (42%) were spontaneous miscarriages, and nine (13%) were therapeutic. Of the 258 deliveries, 250 (97%) were live deliveries, four (2%) were stillbirths, and the status of delivery was unknown for the remaining four (2%). Of the 250 live deliveries, 193 (77%) were term deliveries (gestational period > 37 weeks), 45 (18%) were preterm deliveries (gestational period , 37 weeks), and 62% of the infants had normal birthweights (i.e. 3,4 kg). Neonatal abnormalities were recorded for 23 (9%) of the infants with no apparent pattern in type or severity. Conclusion, The results of this study suggest that foetal exposure to cabergoline through early pregnancy does not induce any increase in the risk of miscarriage or foetal malformation. [source] Activation of Pain by SumatriptanHEADACHE, Issue 9 2003DTM&H, David M. Coulter MB Objective.,To demonstrate that sumatriptan may induce activation or aggravation of pain at sites of inflammation caused by trauma or disease. Methods.,Case reports from the national pharmacovigilance centers of 2 countries, The Netherlands and New Zealand, are presented. These reports come from programs that use 2 methodologies to monitor drugs for adverse reactions: spontaneous reporting and a prospective observational cohort study. The potential mechanisms for pain production by sumatriptan are discussed in detail. Results.,Thirteen case reports of activation of pain by sumatriptan following injury and 8 associated with inflammatory diseases are presented. Most patients had one or more positive rechallenges. This type of reaction occurred at a higher rate with the subcutaneous formulation than with the oral preparation. Pain mostly was severe but short-lasting; pain was prolonged in some patients with inflammatory disease. Conclusions.,A strong association has been demonstrated between the use of sumatriptan and the production of pain at sites of inflammation, and there is a plausible pharmacological mechanism for this reaction. Pain activation may be a class effect of the selective serotonergic agonists used in the treatment of migraine. [source] Insect nicotinic acetylcholine receptor agonists as flea adulticides in small animalsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2010D. T. VO Vo, D. T., Hsu, W. H., Abu-Basha, E. A., Martin, R. J. Insect nicotinic acetylcholine receptor agonists as flea adulticides in small animals. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365-2885.2010.01160.x. Fleas are significant ectoparasites of small animals. They can be a severe irritant to animals and serve as a vector for a number of infectious diseases. In this article, we discuss the pharmacological characteristics of four insect nicotinic acetylcholine receptor (nAChR) agonists used as flea adulticides in dogs and cats, which include three neonicotinoids (imidacloprid, nitenpyram, and dinotefuran) and a macrocyclic lactone (spinosad). Insect nAChR agonists are one of the most important classes of insecticides, which are used to control sucking insects on both plants and animals. These novel compounds provide a new approach for practitioners to safely and effectively eliminate adult fleas. [source] ,2 -Agonists as analgesic agentsMEDICINAL RESEARCH REVIEWS, Issue 2 2009Maria Paola Giovannoni Abstract It is well known that norepinephrine is involved in the control of pain by modulating pain-related responses through various pathways. ,2 -Adrenergic agonists have a well-established analgesic profile and, in the recent years, have found a wider application, in particular as adjunct to anesthetics and analgesics in perioperative settings. This review analyzes the ,2 -agonists currently in clinical use, starting from the prototype Clonidine, as well as the most promising and studied molecules. In addition, an overview of the imidazoles, imidazolines, and hydroxyethyl-thioureas derivatives published in both the open and patented literature is presented, providing chemical description and pharmacological data. Finally, the most commonly ,2 -agonists used in veterinary medicine are described. © 2008 Wiley Periodicals, Inc. Med Res Rev, 29, No. 2, 339,368, 2009 [source] Involvement of ,-opioid receptors in visceral nociception in miceNEUROGASTROENTEROLOGY & MOTILITY, Issue 10 2008M. H. Larsson Abstract, It has been shown that the behavioural responses to chemically evoked visceral nociception are increased in transgenic mice lacking the ,-opioid receptor (KOR). The aim of the present study was to evaluate the contribution of KOR in mechanically evoked visceral pain by performing colorectal distension (CRD) and monitoring the subsequent visceromotor response (VMR) in control mice (KOR+/+) and in mice lacking KOR (KOR,/,). Pseudo-affective visceral pain responses were evoked in conscious mice using increasing (10,80 mmHg) and repeated (12,×,55,mmHg) phasic CRD paradigms. The resulting VMR was determined by monitoring the electromyographic activity of the abdominal muscle. The increasing and repeated CRD paradigms, respectively, evoked similar responses in both KOR+/+ and KOR,/, mice. The selective KOR-agonists U-69593 (5 and 25 mg kg,1, s.c.) and asimadoline (25 mg kg,1, s.c.) significantly decreased the VMR in KOR+/+ mice, while having no effect in KOR,/, mice. In contrast, the selective ,-opioid receptor agonist fentanyl significantly reduced the VMR in both types of mice and appeared more efficacious in KOR,/, mice. The opioid receptor antagonist naloxone (0.3,30 mg kg,1 s.c.) did not affect the response to CRD in C57BL/6 mice at any dose tested. In conclusion, the data confirm that the KOR agonists used in this study inhibit the VMR to CRD in mice by acting via KOR receptors. In addition, the data suggest that the endogenous opioid system is not likely to modulate the VMR to mechanically evoked visceral pain in mice. [source] Phosphatidylserine exposure and other apoptotic-like events in Bernard-Soulier syndrome platelets,AMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2010Margaret L. Rand In the Bernard-Soulier syndrome (BSS), the giant platelets are said to have increased phosphatidylserine (PS) surface exposure in the resting state and shortened survival in the circulation. When normal platelets are activated, they undergo many biochemical and morphological changes, some of which are apoptotic. Herein, we investigated apoptotic-like events in BSS platelets upon activation, specifically, PS exposure, microparticle (MP) formation, cell shrinkage, and loss of mitochondrial inner membrane potential (,,m). Platelets from two unrelated BSS patients were examined in whole blood; agonists used were collagen, thrombin, PAR1- or PAR4-activating peptides (APs), or combinations of collagen with thrombin, and the PAR-APs. Flow cytometry was used to measure PS exposure (annexin A5 binding), platelet-derived MPs (forward scatter; events <0.75 ,m size), and ,,m (TMRM fluorescence). PS exposure was increased on resting and activated BSS platelets, and this was independent of the platelet size. MP formation by BSS platelets was generally enhanced. Cell shrinkage occurred on activation to form smaller, PS-exposing platelets in BSS and controls. A proportion of PS-exposing BSS and control platelets exhibited ,,m loss, but unlike controls, there was also loss of ,,m in the BSS platelets not exposing PS. Thus, BSS platelets undergo apoptotic-like events upon activation, with PS exposure and MP formation being enhanced. These events may play a role in the shortened survival in BSS, as well as affecting thrombin generation. Am. J. Hematol. 85:584,592, 2010. © 2010 Wiley-Liss, Inc. [source] | |||||||||||||