《药理学》课程PPT教学课件（Efferent Sys）12 antidepression

Antidepressants

Antidepressants

Affective disorders and antidepressantsAffective disorders involve a disturbance of mood( cognitive / emotional ) associated with changes inbehavior, energy, appetite, and sleep (biologicalsymptoms).There are two types of affective disordersUnipolar affective disorders1. Maniawhich is characterized by euphoria, increasedmotor activity, flight of ideas, and grandiose self-confidence

Affective disorders and antidepressants Affective disorders involve a disturbance of mood ( cognitive / emotional ) associated with changes in behavior, energy, appetite, and sleep (biological symptoms). There are two types of affective disorders Unipolar affective disorders 1. Mania which is characterized by euphoria, increased motor activity, flight of ideas, and grandiose self￾confidence

2. depressionwhich is characterized by misery, malaise.despair, guilt, apathy, indeciseness, low energyand fatigue, changes in sleeping pattern, loss ofappetite, and suicidal thoughtsBipolar affective disordersBipolar affective disorder presents with mood andbehavior oscillating between depression andmania, and thus is also known as mania-depressivedisorder

2. depression which is characterized by misery, malaise, despair, guilt, apathy, indeciseness, low energy and fatigue, changes in sleeping pattern, loss of appetite, and suicidal thoughts Bipolar affective disorders Bipolar affective disorder presents with mood and behavior oscillating between depression and mania, and thus is also known as mania￾depressive disorder

Monoaminetheory of depressiondepression may be associated with decreasedfunctional amine-dependent synaptic transmission.includes NA and 5-HT, dopamineThe original hypothesis of depressionStated that depression was due to a functional deficitof these transmitter amines, while conversely maniawas caused by an excess

Monoamine theory of depression depression may be associated with decreased functional amine-dependent synaptic transmission. includes NA and 5-HT, dopamine. The original hypothesis of depression Stated that depression was due to a functional deficit of these transmitter amines, while conversely mania was caused by an excess

Other systems maybe involvedin depression#The GABA (Gamma-Aminobutyric acid) systems#The neuropeptide systems, particularlyvasopressin and the endogenous opiates#Secondary-messenger systems also appear tohave a crucial role in some treatments

Other systems may be involved in depression # The GABA (Gamma-Aminobutyric acid) systems # The neuropeptide systems, particularly vasopressin and the endogenous opiates # Secondary-messenger systems also appear to have a crucial role in some treatments

ClassexamplesMode of actionTricyclicNonselective blockers ofAmitriptylineantidepressantsmonoamine uptakeimipramine(TCAs)FluoxetineSelective blocker of5-HTSpecific serotoninreuptake inhibitorsreuptakeParoxetinesertraline5-HT and NASelective blockers of 5-HTvenlafaxineand NAreuptake inhibitorsPhenelzineMonoamineoxidaseNon-competitive,noninhibitor(MAO)selective,irreversibletranylcypromineblockers Of MAOAtypicalMianserinAct by various mechanismstrazodonethat are poorly understood

Class examples Mode of action Tricyclic antidepressants (TCAs) Amitriptyline imipramine Nonselective blockers of monoamine uptake Specific serotonin reuptake inhibitors Fluoxetine Paroxetine sertraline Selective blocker of 5-HT reuptake 5-HT and NA reuptake inhibitors venlafaxine Selective blockers of 5-HT and NA Monoamine oxidase inhibitor(MAO) Phenelzine tranylcypromine Non-competitive, non￾selective, irreversible blockers Of MAO Atypical Mianserin trazodone Act by various mechanisms that are poorly understood

TricyclicAntidepressants-AmitriptylineandimipraminePharmacologic effects and mechanismofaction1. CNS:To normal human being, imipramine induces fatigue,drowsiness, and the person cannot concentrate his mind.For depression patients, the tricyclic compounds elevatemood, increase alertness and improve appetite, sleep.The appearance of antidepressant effects typicallyrequires administration of the drug for several weeks

Tricyclic Antidepressants -Amitriptyline and imipramine Pharmacologic effects and mechanism of action 1. CNS: To normal human being, imipramine induces fatigue, drowsiness, and the person cannot concentrate his mind. For depression patients, the tricyclic compounds elevate mood, increase alertness and improve appetite, sleep. The appearance of antidepressant effects typically requires administration of the drug for several weeks

Mechanism:Tricyclics block the amine (norepinephrine andserotonin) reuptake pumps and potentiate thec amines.Suchan actionactionsofbiogenicofpermitssalongersojournpresumablyneurotransmitter at the receptor site

Mechanism: Tricyclics block the amine (norepinephrine and serotonin) reuptake pumps and potentiate the actions of biogenic amines. Such an action presumably permits a longer sojourn of neurotransmitter at the receptor site

InhibitionofnerveterminalNEneuronaluptakesystemHIncreaseinsynapticconcentrationsofNE↓Desensitizationofnerveterminal α2-adrenoceptors一IncreaseinneuronalNEreleaseHFurtherincreaseinsynapticconcentrationsofNE1Desensitizationofpostsynapticβ-adrenoceptorswithnochangeinpostsynapticαy-adrenoceptorsensitivityFIGURE33.2Cascade of adaptive changes occurring at norepinephrine(NE)synapsesfollowingchronicTCAdrugtreatment

Synthesis andDegradation:L-TRYPTOPHANHYDROXYLATION5-OH TRYPTOPHANDECARBOXYLATIONMELATONINS-OHTRYPTAMINEETYLATIONTHYLATIONdal enty)MAOSTORAGESUVESICLES-HIAA5-HT?URINETRANSPORTERGiGq5-HT15-HT35-HT2Figure 3:Synthesis, degradation and receptors for5-HT

Figure 3: Synthesis, degradation and receptors for 5-HT