The Adrenergic Control of Lower Esophageal Sphincter Function: an EXPERIMENTAL MODEL of DENERVATION SUPERSENSITIVITY
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Adrenergic Antagonist
PHARMACOLOGY Adrenergic antagonist OBJECTIVES: • Describe the different classifications for drugs that can block sympathetic nervous system. •Describe the kinetics, dynamics, uses and side effects of alpha adrenergic drugs. • Identify Difference between selective and non selective alpha blockers. • Know the difference between tamsulosin and other selective alpha receptor blockers. •Identify the different classifications for beta receptors blockers. •Describe the kinetics, dynamics, uses and side effects of beta adrenergic drugs. •Know the preferable drug for diseases as hypertension, glaucoma, arrythmia, myocardial infarction, anxiety, migraine and ect…. • Important. • Extra notes It’s a recall, if you know it you can skip it! Adrenergic receptors Adrenergic receptors Dopaminergic adrenoceptors adrenoceptors α− β− receptors β3 α1 α2 β1 β2 e.g. D1 α1 β2 β1 β3 Post-synaptic excitatory in function (cause inhibitory in function excitatory in In adipose contraction) except in GIT. (cause relaxation) function, present tissue mainly in heart Present mainly in smooth muscles. Contraction of pregnant Relaxation of the uterus ↑ heart rate: ↑ lipolysis uterus. (Delay premature labor) + chronotropic ↑ free fatty effect, Vasoconstriction of skin & Relaxation of skeletal & acids. Tachycardia peripheral blood vessels coronary blood vessels →increased peripheral (vasodilatation) ↑ force of → resistance hypertension. contraction : Relaxation of GIT muscles & urinary bladder’s muscles. + inotropic effect Contraction of GIT sphincter (constipation) & urinary -
M100907, a Serotonin 5-HT2A Receptor Antagonist and Putative Antipsychotic, Blocks Dizocilpine-Induced Prepulse Inhibition Defic
M100907, a Serotonin 5-HT2A Receptor Antagonist and Putative Antipsychotic, Blocks Dizocilpine-Induced Prepulse Inhibition Deficits in Sprague–Dawley and Wistar Rats Geoffrey B. Varty, Ph.D., Vaishali P. Bakshi, Ph.D., and Mark A. Geyer, Ph.D. a In a recent study using Wistar rats, the serotonergic 5-HT2 1 receptor agonist cirazoline disrupts PPI. As risperidone a receptor antagonists ketanserin and risperidone reduced the and M100907 have affinity at the 1 receptor, a final study disruptive effects of the noncompetitive N-methyl-D- examined whether M100907 would block the effects of aspartate (NMDA) antagonist dizocilpine on prepulse cirazoline on PPI. Risperidone partially, but inhibition (PPI), suggesting that there is an interaction nonsignificantly, reduced the effects of dizocilpine in Wistar between serotonin and glutamate in the modulation of PPI. rats, although this effect was smaller than previously In contrast, studies using the noncompetitive NMDA reported. Consistent with previous studies, risperidone did antagonist phencyclidine (PCP) in Sprague–Dawley rats not alter the effects of dizocilpine in Sprague–Dawley rats. found no effect with 5-HT2 antagonists. To test the hypothesis Most importantly, M100907 pretreatment fully blocked the that strain differences might explain the discrepancy in effect of dizocilpine in both strains; whereas SDZ SER 082 these findings, risperidone was tested for its ability to had no effect. M100907 had no influence on PPI by itself reduce the PPI-disruptive effects of dizocilpine in Wistar and did not reduce the effects of cirazoline on PPI. These and Sprague–Dawley rats. Furthermore, to determine studies confirm the suggestion that serotonin and glutamate which serotonergic receptor subtype may mediate this effect, interact in modulating PPI and indicate that the 5-HT2A the 5-HT2A receptor antagonist M100907 (formerly MDL receptor subtype mediates this interaction. -
Guanfacine Extended Release for ADHD
Out of the Pipeline p Guanfacine extended release for ADHD Floyd R. Sallee, MD, PhD uanfacine extended release (GXR)— Table 1 α Once-daily a selective -2 adrenergic agonist Guanfacine extended release: GFDA-approved for the treatment formulation may of attention-defi cit/hyperactivity disor- Fast facts improve adherence der (ADHD)—has demonstrated effi cacy Brand name: Intuniv and control for inattentive and hyperactive/impulsive Indication: Attention-defi cit/hyperactivity symptoms across disorder symptom domains in 2 large trials lasting® Dowden Health Media a full day 8 and 9 weeks.1,2 GXR’s once-daily formu- Approval date: September 3, 2009 lation may increase adherence and deliver Availability date: November 2009 consistent control of symptomsCopyright across a For personalManufacturer: use Shire only full day (Table 1). Dosing forms: 1-mg, 2-mg, 3-mg, and 4-mg extended-release tablets Recommended dosage: 0.05 to 0.12 mg/kg Clinical implications once daily GXR exhibits enhancement of noradren- ergic pathways through selective direct receptor action in the prefrontal cortex.3 brain believed to play a major role in at- This mechanism of action is different from tentional and organizational functions that that of other FDA-approved ADHD medi- preclinical research has linked to ADHD.3 cations. GXR can be used alone or in com- The postsynaptic α-2A receptor is bination with stimulants or atomoxetine thought to play a central role in the opti- for treating complex ADHD, such as cases mal functioning of the PFC as illustrated accompanied by oppositional features and by the “inverted U hypothesis of PFC ac- emotional dysregulation or characterized tivation.”4 In this model, cyclic adenos- by partial stimulant response. -
Covalent Agonists for Studying G Protein-Coupled Receptor Activation
Covalent agonists for studying G protein-coupled receptor activation Dietmar Weicherta, Andrew C. Kruseb, Aashish Manglikb, Christine Hillera, Cheng Zhangb, Harald Hübnera, Brian K. Kobilkab,1, and Peter Gmeinera,1 aDepartment of Chemistry and Pharmacy, Friedrich Alexander University, 91052 Erlangen, Germany; and bDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305 Contributed by Brian K. Kobilka, June 6, 2014 (sent for review April 21, 2014) Structural studies on G protein-coupled receptors (GPCRs) provide Disulfide-based cross-linking approaches (17, 18) offer important insights into the architecture and function of these the advantage that the covalent binding of disulfide-containing important drug targets. However, the crystallization of GPCRs in compounds is chemoselective for cysteine and enforced by the active states is particularly challenging, requiring the formation of affinity of the ligand-pharmacophore rather than by the elec- stable and conformationally homogeneous ligand-receptor com- trophilicity of the cross-linking function (19). We refer to the plexes. Native hormones, neurotransmitters, and synthetic ago- described ligands as covalent rather than irreversible agonists nists that bind with low affinity are ineffective at stabilizing an because cleavage may be promoted by reducing agents and the active state for crystallogenesis. To promote structural studies on disulfide transfer process is a reversible chemical reaction the pharmacologically highly relevant class -
The Importance of Serotonergic and Adrenergic Receptors for the Induction and Expression of One-Trial Cocaine-Induced Behavioral Sensitization" (2016)
California State University, San Bernardino CSUSB ScholarWorks Electronic Theses, Projects, and Dissertations Office of aduateGr Studies 12-2016 THE IMPORTANCE OF SEROTONERGIC AND ADRENERGIC RECEPTORS FOR THE INDUCTION AND EXPRESSION OF ONE- TRIAL COCAINE-INDUCED BEHAVIORAL SENSITIZATION Krista N. Rudberg California State University - San Bernardino Follow this and additional works at: https://scholarworks.lib.csusb.edu/etd Part of the Biological Psychology Commons, and the Pharmacology Commons Recommended Citation Rudberg, Krista N., "THE IMPORTANCE OF SEROTONERGIC AND ADRENERGIC RECEPTORS FOR THE INDUCTION AND EXPRESSION OF ONE-TRIAL COCAINE-INDUCED BEHAVIORAL SENSITIZATION" (2016). Electronic Theses, Projects, and Dissertations. 420. https://scholarworks.lib.csusb.edu/etd/420 This Thesis is brought to you for free and open access by the Office of aduateGr Studies at CSUSB ScholarWorks. It has been accepted for inclusion in Electronic Theses, Projects, and Dissertations by an authorized administrator of CSUSB ScholarWorks. For more information, please contact [email protected]. THE IMPORTANCE OF SEROTONERGIC AND ADRENERGIC RECEPTORS FOR THE INDUCTION AND EXPRESSION OF ONE-TRIAL COCAINE- INDUCED BEHAVIORAL SENSITIZATION A Thesis Presented to the Faculty of California State University, San Bernardino In Partial Fulfillment of the Requirements for the Degree Master of Arts in General/Experimental Psychology by Krista Nicole Rudberg December 2016 THE IMPORTANCE OF SEROTONERGIC AND ADRENERGIC RECEPTORS FOR THE INDUCTION AND EXPRESSION OF ONE-TRIAL COCAINE- INDUCED BEHAVIORAL SENSITIZATION A Thesis Presented to the Faculty of California State University, San Bernardino by Krista Nicole Rudberg December 2016 Approved by: Sanders McDougall, Committee Chair, Psychology Cynthia Crawford, Committee Member Matthew Riggs, Committee Member © 2016 Krista Nicole Rudberg ABSTRACT Addiction is a complex process in which behavioral sensitization may be an important component. -
Pharmacological Approach to Sleep Disturbances in Autism Spectrum Disorders with Psychiatric Comorbidities: a Literature Review
medical sciences Review Pharmacological Approach to Sleep Disturbances in Autism Spectrum Disorders with Psychiatric Comorbidities: A Literature Review Sachin Relia 1,* and Vijayabharathi Ekambaram 2,* 1 Department of Psychiatry, University of Tennessee Health Sciences Center, 920, Madison Avenue, Suite 200, Memphis, TN 38105, USA 2 Department of Psychiatry, University of Oklahoma Health Sciences Center, 920, Stanton L Young Blvd, Oklahoma City, OK 73104, USA * Correspondence: [email protected] (S.R.); [email protected] (V.E.); Tel.: +1-901-448-4266 (S.R.); +1-405-271-5251 (V.E.); Fax: +1-901-297-6337 (S.R.); +1-405-271-3808 (V.E.) Received: 15 August 2018; Accepted: 17 October 2018; Published: 25 October 2018 Abstract: Autism is a developmental disability that can cause significant emotional, social and behavioral dysfunction. Sleep disorders co-occur in approximately half of the patients with autism spectrum disorder (ASD). Sleep problems in individuals with ASD have also been associated with poor social interaction, increased stereotypy, problems in communication, and overall autistic behavior. Behavioral interventions are considered a primary modality of treatment. There is limited evidence for psychopharmacological treatments in autism; however, these are frequently prescribed. Melatonin, antipsychotics, antidepressants, and α agonists have generally been used with melatonin, having a relatively large body of evidence. Further research and information are needed to guide and individualize treatment for this population group. Keywords: autism spectrum disorder; sleep disorders in ASD; medications for sleep disorders in ASD; comorbidities in ASD 1. Introduction Autism is a developmental disability that can cause significant emotional, social, and behavioral dysfunction. According to the Diagnostic and Statistical Manual (DSM-V) classification [1], autism spectrum disorder (ASD) is characterized by persistent deficits in domains of social communication, social interaction, restricted and repetitive patterns of behavior, interests, or activities. -
F3-Adrenergic Antagonist (Receptors/Cyclic AMP/Aminobenzylpropranolol/Iodohydroxybenzylpindolol/Isoproterenol) WESLEY L
Proc. Natl. Acad. Sci. USA Vol. 76, No. 12, pp. 6401-6405, December 1979 Cell Biology Quantitative relationship between 3-adrenergic receptor number and physiologic responses as studied with a long-lasting f3-adrenergic antagonist (receptors/cyclic AMP/aminobenzylpropranolol/iodohydroxybenzylpindolol/isoproterenol) WESLEY L. TERASAKI, JOEL LINDEN, AND GARY BROOKER* Department of Pharmacology, School of Medicine, University of Virginia, Charlottesville, Virginia 22908 Communicated by Paul Greengard, August 20, 1979 ABSTRACT The aminobenzyl analog of propranolol, atrium when f3-adrenergic receptor number is selectively de- 1- (p-amino-a,a-dimethylphenethylamino)-3(1-naphthoxy)2- creased. To investigate this problem, a new propanol, was synthesized and found tobe a potent B-adrenergic f3-adrenergic blocking agent. The fl-adrenergic receptors of cultured rat C6 blocking agent, 1-(p-amino-a,a-dimethylphenethylamino- glioma cells (2B clone) as assessed by [' 51]iodohydroxybenzyl- 3-(1-naphthoxy)-2-propanol (aminobenzylpropranolol), was pindolol binding were decreased 50 and >95% afterpretreat- synthesized. It was found to be a selective agent for the elimi- ment with 8 nM and 1 ,M aminobenzylpropranolol, respec- nation of cellular /3-adrenergic receptors. tively. Unlike propranolol, aminobenzylpropranolol displayed a prolonged blockade of receptors that was maintained during several hours of washing. [121s]Iodohydroxybenzylpindolol MATERIALS AND METHODS saturation binding experiments in cells exposed to aminoben- Tissue Culture. C6 rat glioma cells, 2B subclone (7), were zylpropranolol and subsequently washed indicated that the compound effectively diminished receptor number with no grown in monolayer cultures as described (1) in 16-mm plastic change in the affinity of the remaining receptors for iodohy- cluster dishes. In all experiments, the cells were changed from droxybenzylpindolol. -
Mutation of the 2A-Adrenoceptor Impairs Working Memory Performance and Annuls Cognitive Enhancement by Guanfacine
The Journal of Neuroscience, October 1, 2002, 22(19):8771–8777 ␣ Mutation of the 2A-Adrenoceptor Impairs Working Memory Performance and Annuls Cognitive Enhancement by Guanfacine Jenna S. Franowicz,1 Lynn E. Kessler,1 Catherine M. Dailey Borja,1 Brian K. Kobilka,2 Lee E. Limbird,3 and Amy F. T. Arnsten1 1Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, 2Howard Hughes Medical Institute and Departments of Medicine and Molecular and Cellular Physiology, Stanford University, Palo Alto, California 94305, and 3Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 Norepinephrine strengthens the working memory, behavioral cortical damage or a spatial discrimination control task with inhibition, and attentional functions of the prefrontal cortex similar motor and motivational demands but no dependence on ␣ ␣ through actions at postsynaptic 2-adrenoceptors ( 2-AR). The prefrontal cortex. The effects of guanfacine on performance of ␣ 2-AR agonist guanfacine enhances prefrontal cortical func- the delayed alternation task were assessed in additional groups ␣ tions in rats, monkeys, and human beings and ameliorates of wild-type versus 2A-AR mutant mice. We observed that ␣ prefrontal cortical deficits in patients with attention deficit hy- functional loss of the 2A-AR subtype, unlike knock-out of the ␣ peractivity disorder. The present study examined the subtype of 2C-AR subtype, weakened performance of the prefrontal cor- ␣ 2-AR underlying these beneficial effects. Because there are no tical task without affecting learning and resulted in loss of the ␣ ␣ ␣ selective 2A-AR, 2B-AR, or 2C-AR agonists or antagonists, beneficial response to guanfacine. These data demonstrate the ␣ genetically altered mice were used to identify the molecular importance of 2A-AR subtype stimulation for the cognitive target of the action of guanfacine. -
Synergistic Action of 5-HT2A Antagonists and Selective Serotonin Reuptake Inhibitors in Neuropsychiatric Disorders
Neuropsychopharmacology (2003) 28, 402–412 & 2003 Nature Publishing Group All rights reserved 0893-133X/03 $25.00 www.neuropsychopharmacology.org Synergistic Action of 5-HT2A Antagonists and Selective Serotonin Reuptake Inhibitors in Neuropsychiatric Disorders ,1 2 3 2 Gerard J Marek* , Linda L Carpenter , Christopher J McDougle and Lawrence H Price 1Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA; 2Department of Psychiatry and Human, Brown Medical School, Mood 3 Disorders Program, Behavior, Butler Hospital, Providence, RI, USA; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA Recently, the addition of drugs with prominent 5-HT2 receptor antagonist properties (risperidone, olanzapine, mirtazapine, and mianserin) to selective serotonin reuptake inhibitors (SSRIs) has been shown to enhance therapeutic responses in patients with major depression and treatment-refractory obsessive–compulsive disorder (OCD). These 5-HT antagonists may also be effective in 2 ameliorating some symptoms associated with autism and other pervasive developmental disorders (PDDs). At the doses used, these drugs would be expected to saturate 5-HT2A receptors. These findings suggest that the simultaneous blockade of 5-HT2A receptors and activation of an unknown constellation of other 5-HT receptors indirectly as a result of 5-HT uptake inhibition might have greater therapeutic efficacy than either action alone. Animal studies have suggested that activation of 5-HT1A and 5-HT2C receptors may counteract the effects of activating 5-HT2A receptors. Additional 5-HT receptors, such as the 5-HT1B/1D/5/7 receptors, may similarly counteract the effects of 5-HT receptor activation. These clinical and preclinical observations suggest that the combination of highly 2A selective 5-HT antagonists and SSRIs, as well as strategies to combine high-potency 5-HT receptor and 5-HT transporter blockade in 2A 2A a single compound, offer the potential for therapeutic advances in a number of neuropsychiatric disorders. -
Study of Methyl Dopa Versus Labetalol in Management of Preeclampsia and Gestational Hypertension
logy & Ob o st ec e tr n i y c s G Dharwadkar et al., Gynecol Obstet (Sunnyvale) 2014, 4:9 Gynecology & Obstetrics DOI; 10.4172/2161-0932.1000242 ISSN: 2161-0932 Research Article Open Access Study of Methyl Dopa Versus Labetalol in Management of Preeclampsia and Gestational Hypertension Dharwadkar MN1, Kanakamma MK1, Dharwadkar SN2*, Rajagopal K1, Gopakumar C3, Divya James Fenn J4 and Balachandar V3,5 1Department of Obstetrics and Gynaecology, Yenepoya Medical College and teaching Hospital, Yenepoya University, Deralakatte, Mangalore, Karnataka 575022, India 2Department of Zoology, K.L.E’s. S. Nijalingappa College, KLE Medical University (Health), Bangalore, Karnataka 560010, India 3Department of Human Genetics Molecular Biology, Bharathiar University, Coimbatore, India 4Post Graduate Student, Department of Obstetrics and Gynaecology, Sree Balaji Medical College and Hospital, Chennai 600044, Tamil Nadu, India 5Human Molecular Genetics Laboratory, Department of Zoology, Bharathiar University, Coimbatore, India Abstract Objective: To assess the efficacy and safety of labetalol compared with methyldopa in the management of mild and moderate cases of pregnancy-induced hypertension (PIH). Methods: Eighty patients with PIH were randomly allocated to receive either labetalol (group A) or methyldopa (group B). Administration of drugs with respect to Age, Gravid Status, Blood Pressure, Urine albumin Levels, Side Effects, Drug dosage, Additional Treatment, Prolongation of Pregnancy, New born Screening Test (NST), mode of termination, Indication of caesarean section, Perinatal safety and APGAR scores were studied. The statistical level of significance was taken at P<0.05. Results: A labetalol has been very effective in control as well as earlier onset of action in patients with methyl dopa. -
Oral Phentolamine: an Alpha-1, Alpha-2 Adrenergic Antagonist for the Treatment of Erectile Dysfunction
International Journal of Impotence Research (2000) 12, Suppl 1, S75±S80 ß 2000 Macmillan Publishers Ltd All rights reserved 0955-9930/00 $15.00 www.nature.com/ijir Oral phentolamine: an alpha-1, alpha-2 adrenergic antagonist for the treatment of erectile dysfunction I Goldstein1 1Department of Urology, Boston University School of Medicine, Boston, MA, USA Phentolamine mesylate is an alpha-1 and alpha-2 selective adrenergic receptor antagonist which has undergone clinical trials for erectile dysfunction treatment. Biochemical and physiological studies in human erectile tissue have revealed a high af®nity of phentolamine for alpha-1 and alpha-2 adrenergic receptors. Based on pharmacokinetic studies, it is suggested that 30±40 min following oral ingestion of 40 or 80 mg of phentolamine (Vasomax), the mean plasma phentolamine concentrations are suf®cient to occupy the alpha-1 and -2 adrenergic receptors in erectile tissue and thereby result in inhibition of adrenergic-mediated physiologic activity. In large multi-center, placebo-controlled pivotal phase III clinical trials, the mean change in the erectile function domain of the International Index of Erectile Function scores (Questions 1±5 and 15) from screening to the end of treatment was signi®cantly higher following use of active drug (40 mg and 80 mg) compared to placebo. Three to four times as many patients receiving phentolamine reported being satis®ed or very satis®ed compared with those receiving placebo. At doses of 40 mg and 80 mg respectively, 55% and 59% of men were able to achieve vaginal penetration with 51% and 53% achieving penetration on 75% of attempts. -
α2-Adrenoceptor and 5-Ht3 Serotonin Receptor
Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2012 α2-ADRENOCEPTOR AND 5-HT3 SEROTONIN RECEPTOR LIGANDS AS POTENTIAL ANALGESIC ADJUVANTS Genevieve Alley Virginia Commonwealth University Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Pharmacy and Pharmaceutical Sciences Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/2867 This Dissertation is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. © Genevieve Sirles Alley 2012 All Rights Reserved i α2-ADRENOCEPTOR AND 5-HT3 SEROTONIN RECEPTOR LIGANDS AS POTENTIAL ANALGESIC ADJUVANTS A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. by Genevieve Sirles Alley Bachelor of Science in Biology, Virginia Commonwealth University 2005 Director: Małgorzata Dukat, Ph.D. Associate Professor, Department of Medicinal Chemistry Virginia Commonwealth University Richmond, Virginia August 2012 ii ACKNOWLEDGMENT First, I would like to thank Dr. Małgorzata Dukat for her continued assistance and advice throughout my studies. This guidance has helped me better understand and appreciate medicinal chemistry. Also, a special thanks is given to both Dr. Dukat and Dr. Richard A. Glennon for their constant quizzing during group meetings, which not only helped me recongnize what I did not already understand, but also, improved my ability to devise potential solutions for future research problems. Furthermore, I could not have successfully completed this dissertation work without the help of Dr.