logging in or signing up screening of anti depressant sayantisau Download Post to : URL : Related Presentations : Let's Connect Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Copy embed code: Embed: Flash iPad Dynamic Copy Does not support media & animations Automatically changes to Flash or non-Flash embed WordPress Embed Customize Embed URL: Copy Thumbnail: Copy The presentation is successfully added In Your Favorites. Views: 236 Category: Science & Tech.. License: All Rights Reserved Like it (0) Dislike it (0) Added: September 26, 2013 This Presentation is Public Favorites: 1 Presentation Description No description available. Comments Posting comment... Premium member Presentation Transcript PowerPoint Presentation: 1 WELCOME PowerPoint Presentation: PRESENTED BY: MISS SAYANTI SAU I M. PHARM DEPT OF PHARMACOLOGY PESCP, BANGALORE SCREENING METHODS OF ANTIDEPRESSANTS UNDER GUIDANCE OF: MRS. MEENU SINGH ASST. PROFESSOR DEPT OF PHARMACOLOGY PESCP, BANGALORE OBJECTIVE: OBJECTIVE To understand the concepts behind Antidepressants and to reproduce the concepts of screening and clinical evaluation of antidepressants practically as well as theoretically. PowerPoint Presentation: WHAT IS DEPRESSION Depression is the most common affective mental disorder. Defined as disorder of mood rather than disturbances of thought or cognition. It is psychobiologic phenomena resulting from abnormal brain mechanism. Second leading cause of death in India. one lakh deaths occurs every year. Antidepressants are second most prescribed drugs in US. It is estimated that 1 in 4 women and 1 in 10 men suffers from depression. DEPRESSION: DEPRESSION Worthlessness Low mood Loss of interest Disturbed sleep Disturbed appetite Low energy Sadness Poor concentration Hopelessness 5 PowerPoint Presentation: Gender Age Chronic stress/lifestyle Poverty Chronic health problems Lack of social support Risk factors Low mood, low self esteem, F eeling of guilts L oss of motivation A nhedonia Retardation of thought and action Loss of libido Sleep disturbances Loss of appetite Symptoms SIGNS AND SYMPTOMS: SIGNS AND SYMPTOMS Feelings of helplessness and hopelessness : A bleak outlook—nothing will ever get better and there’s nothing you can do to improve your situation. Loss of interest in daily activities : No interest in or ability to enjoy former hobbies, pastimes, social activities or sex. Appetite or weight changes: Significant weight loss or weight gain—a change of more than 5% of body weight in a month. 7 PowerPoint Presentation: Psychomotor agitation or retardation: Either feeling “keyed up” and restless or sluggish and physically slowed down. Sleep changes : Either insomnia, especially waking in the early hours of the morning, or oversleeping (also known as hypersomnia ). Loss of energy : Feeling fatigued and physically drained. Even small tasks are exhausting or take longer. Self-loathing : Strong feelings of worthlessness or guilt. Harsh criticism of perceived faults and mistakes. Concentration problems : Trouble focusing, making decisions, or remembering things. 8 PowerPoint Presentation: NEED FOR SCREENING? Severe side effects of the existing drugs. So need for more safe drugs. Need to find more efficacious drugs. PROBLEMS ASSOCIATED WITH SCREENING OF ANTI DEPRESSANTS……. Lack of animal models that resemble depressive illness in humans. Most of the existing models concentrate on monoamine theory of depression only. TYPES OF DEPRESSION: TYPES OF DEPRESSION 1.Major depression :( Unipolar depression ) 2.Bipolar depression 3.Atypical depression 4.Psychotic depression 5.Postpartum depression 6.Premenstrual depression 7.Seasonal depression 10 WHY DEPRESSION IS CAUSED: WHY DEPRESSION IS CAUSED The major cause is deficiency of some neurotransmitters in the brain namely Nor epinephrine and serotonin. When these neurotransmitters don’t delivered correctly between brain cells there will be disruption in communication. This disruption is due to cell hardening to pass the message which is caused by chemical imbalance. 11 ANTIDEPRESSANT: : ANTIDEPRESSANT: These are the drugs which can elevate mood in depressive illness. Antidepressants are drugs used for the treatment of depression and other conditions including anxiety disorders, obsessive compulsive disorder, eating disorders, chronic pain, neuropathic pain and, in some cases, dysmenorrhea , snoring, migraines, attention-deficit hyperactivity disorder (ADHD),substance abuse and sleep disorders. They can be used alone or in combination with other medications. All these drugs affect monoaminergic transmissions in the brain and have other associated properties. CLASSIFICATION: CLASSIFICATION 1. MAO inhibitors: a. Irreversible : Isocarboxazid ,Iproniazid , Phenelzine. b. Reversible : Moclobemide , Clorgyline 2. Triycyclic anti-depressants: A . Noradrenaline and Serotonin reuptake inhibitors(SNRIs): I mipramine, Amipriptyline , Clomipramine B . Noradrenaline reuptake inhibitors(NERIs): D esipramine, A moxapine , R eboxetine,Nor tryptyline 3. Selective Serotonin reuptake inhibitors(SSRIs): Fluoxetine, Paroxetine , Sertraline 4. Atypical antidepressants: Trazodone , Amineptine, Mianserin, Venlafaxine . 13 PowerPoint Presentation: CLASSIFICATION OF ANTIDEPRESSANTS DRUGS PHARMACOLGY:: PHARMACOLGY : MAO is a mitochondrial enzyme involved in the oxidative deamination of biogenic amine MAO-A MAO-B Comprise two structurally related flavin containing enzymes Epinephrine ,Nor adrenaline & Serotonin Phenethylamine Selegline Clorgyline Inhibition of this enzyme system by MAO inhibitor cause a reduction in metabolism & a subsequent increase in the concentration of biogenic amine deaminates inhibition 15 PowerPoint Presentation: MOA OF ACTION OF TCAs: 16 PowerPoint Presentation: MOA OF SSRIs: The selective serotonin reuptake (SSRIs) block neuronal reuptake of serotonin into serotonergic nerve ending. Hence they enhance serotonin levels in the synapse . 17 PowerPoint Presentation: MONOAMINE HYPOTHESIS: First proposed in 1965, states that depression is caused by a functional deficit of monoamine transmitters (NA, 5-HT) at certain sites in brain. Lowered levels of brain derived neurotrophic factor (BDNF) and malfunction of this receptor plays a significant role in depression. Plasma cortisol secretion is high in depressed patients. Recent advances shows that depression may be associated with neuro degeneration and reduced neurogenesis in hippocampus . THEORIES OF DEPRESSION PowerPoint Presentation: LIMITATION OF THIS HYPOTHESIS Antidepressant action produce within hour but, clinical benefit takes several weeks, Amphetamine and cocaine not used as antidepressant despite their ability to facilitate NE transmission. 19 SCREENING METHODS OF ANTIDEPRESSANT DRUG: SCREENING METHODS OF ANTIDEPRESSANT DRUG 20 PowerPoint Presentation: BEHAVIORAL TESTS: TESTS FOR ANTIDEPRESSANT ACTIVITY BASED ON THE MECHANISM OF ACTION: TESTS FOR ANTIDEPRESSANT ACTIVITY BASED ON THE MECHANISM OF ACTION Potentiation of norepinephrine toxicity Compulsive gnawing in mice Apomorphine - induced hypothermia in mice Tetrabenazine antagonism in mice Reserpine induced hypothermia 5-Hydroxytryptophan potentiation in mice 5-Hydroxytryptophan potentiation in rats Yohimbine toxicity enhancement Tryptamine seizure potentiation in rats Serotonin syndrome in rats Hypermotility in olfactory- bulbectomized rats Sexual behavior in male rats 22 BEHAVIORAL DESPAIR ACTIVITY: BEHAVIORAL DESPAIR ACTIVITY Water wheel model Forced swim test IN VIVO METHODS 23 WATER WHEEL MODEL: WATER WHEEL MODEL 24 PowerPoint Presentation: Mice in weight range (20 to 25 g) selected. Randomly divided into 3 groups. Animals are put through a preliminary exam to determine typical no . of rotations of water wheel prior to onset of behavioural despair . Animals are treated with vehicle (control ) , std . drug like imipramine(5-20 mg / kg i.p .) and test drug in various doses and rechallanged on the water wheel . EVALUATION: A potential antidepressant will increase the number of counts of water wheel turns indicating increased effort at escape behaviour . A classical TCA reduce immobility time in this model. But SSRIs are inactive in this test. Method 25 FORCED SWIM TEST: FORCED SWIM TEST This behavior reflects a state of despair which can reduced by several agents which are therapeutically effective in human depression . 26 METHOD: METHOD Male Spargue - Dawley rats(160-180gm) Vertical Plexiglas cylinder (height:40cm diameter:18cm containing 15cmof water maintained at 25 c) They are again placed in the cylinder 24h later and the total duration of immobility is measured during a 5min test. 27 Three groups contains 6 animals: Three groups contains 6 animals TREATMENT GROUP Test drug was administerd before 30 min. I.p route . CONTROL GROUP Vehicle was administered before 30 min. I.p route Antidepressant drugs, but also stimulants like amphetamine and caffeine, reduce duration of immobility. Floating Active swimming Climbing Head shaking STANDARD GROUP Standard drug Imipramine I.p route 28 PowerPoint Presentation: LIMITATION: Antidepressant drugs show paradigm shift within 24 hrs of treatment initiation. High doses of drugs are required. This method is both sensitive & selective for clinically effective antidepressant drugs. The test has been validated by most of the current antidepressant. 29 TAIL SUSPENSION TEST: TAIL SUSPENSION TEST PURPOSE AND RATIONALE: The immobility displayed by rodents when subjected to an unavoidable and inescapable stress has been hypothesized to reflect behavioral despair which in turn may reflect depressive disorders in humans. Clinically effective antidepressants reduce the immobility that mice display after active and unsuccessful attempts to escape when suspended by the tail. 30 METHOD :: METHOD : 20 Male mice (20-25 gm) 2 groups Housed in plastic cages with food and water Drug or vehicle given by i.p route 30 min later mice are suspended on upside down posture 58 cm above a table top approx 1 cm from tail tip. Initially animal tries to escape but is unable to escape & becomes immobile Duration of immobility is recorded for 5 min Mice are considered immobile when they hang passively and completely motionless for at least 1 min 31 PowerPoint Presentation: Two groups TREATMENT GROUP Test drug was administerd before 30 min. I.p route . CONTROL GROUP Vehicle was administered before 30 min. I.p route Antidepressant drugs reduce duration of immobility. 32 PowerPoint Presentation: LIMITATION Agents acting via the serotonergic pathway can be screened using this method. In contrast, MAO inhibitors fail to answer this test. MODERN APPARATUS 33 Tail Suspension Monitor PowerPoint Presentation: 34 BASIC PROCEDURE OF RECEPTOR BINDING ASSAY Isolate the cells with receptors Add radioactive ligand for that receptor in presence and absence of test drugs Count the receptor ligand binding by liquid scintillography . IN VITRO METHODS PowerPoint Presentation: INHIBITION OF NOREPINEPHRINE IN RAT BRAIN SYNAPTOSOMES PURPOSE AND RATIONALE Neuronal reuptake mechanism for nor epinephrine is important process removing and inactivating NE in synaptic cleft .This action is inhibited by many antidepressants. Hypothalamus region uptake the greatest level of NE, so this region is used . 35 PowerPoint Presentation: PROCEDURE : 36 PowerPoint Presentation: : ASSAY: 200 μ l of the tissue suspension+800 μ l of 62.5nM of NE in Krebs- Henselit bicarbonate buffer+20 μ l of drug 3 tubes are taken for each assay and incubated with 20 μ l of vehicle at 0 ° c in an ice bath After incubation all tubes are immediately centrifuged at 4000g for 10 min Pellets are dissolved by adding 1 ml of solubiliser ( Triton+ethanol ) and by aspirating the supernatent fluid. Tubes are vigorously shaken and decanted into scintillation vails and counted in 10ml of scintillation cocktail. Active uptake is diff b/w cpm at 37 °c and 0 °c . 37 PowerPoint Presentation: EVALUATION: 1.Inhibition at each drug concentration is the mean of 3 determinations. 2.IC50 values are derived from log-profit. 38 INHIBITION OF - SEROTONIN UPTAKE IN SYNAPTOSOMES: INHIBITION OF - SEROTONIN UPTAKE IN SYNAPTOSOMES PURPOSE AND RATIONALE Patients with serotoninergic hypofunction constitute a subgroup of depression and claim that altered serotoninergic function determines the mood changes associated with affective disorders. A number of clinically effective antidepressants block the reuptake of 5-HT( 3H-5-HT transport in brain). Therefore the test can be used to detect compounds that inhibit serotonin uptake into rat brain synaptosomes and may be potential antidepressants. 39 PowerPoint Presentation: 40 PROCEDURE TISSUE PREPARATION PowerPoint Presentation: 41 ASSAY METHOD PowerPoint Presentation: EVALUATION: The percent inhibition of each drug concentration is the mean of 3 determinations. IC50 values are calculated from log- probit analyses. Standard drugs, such as chlorimipramine show IC50 values are derived from log profit . 42 CONCLUSION: CONCLUSION Depression is a leading disease now a days. To understand the treatment of various types of depression ,it is necessary to have a detailed knowledge about antidepressant. All antidepressants do not act similar way to understand the pharmacology and to invent more safe and potent drugs different screening models are very important . No animal model will accurately mimic the human suffering of depreesion . So further research on various sreening models are required. Nevertheless, the knowledge gathered from animal studies undoubtedly valuable therapeutically in the future studies. 43 PowerPoint Presentation: Drug Discovery and Evaluation by H. Gerhard Vogel Pharmacological Screening & Evaluation by S.K.Gupta Internet source . Drugs The Straight Facts, Antidepressants REFERENCES : PowerPoint Presentation: 45 PowerPoint Presentation: 46 You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.