Biochemistry of Depression and Commonly Prescribed Antidepressants - PowerPoint PPT Presentation

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Biochemistry of Depression and Commonly Prescribed Antidepressants
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Biochemistry of Depression and Commonly Prescribed Antidepressants

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  1. Biochemistry of Depression and Commonly Prescribed Antidepressants Tricia Hill Biochemistry 7 December 2006

  2. Abraham Lincoln “I am now the most miserable man living. If what I feel were equally distributed to the whole human family, there would be not one cheerful face on earth. Whether I shall ever be better, I cannot tell. I awfully forebode I shall not. To remain as I am is impossible. I must die or be better it appears to me.”

  3. Purpose of Research • Recent issues regarding increased use of antidepressants • Concern about long-term effects of antidepressants • Previous rise in U.S. suicide rates • More recent slight decline, except individuals age 10 to 45 • Publications of books about mental illness and psychopharmacology

  4. Depression • Has been stated that antidepressants only control symptoms of depression • Diagnosis of illness requires persistence of symptoms for • Some symptoms include: • feelings of loneliness, sadness, hopelessness, or despair • changes in sleep or eating patterns • excessive irritability or anger • lack of confidence • physical exhaustion much of the time • suicidal thoughts or attempts

  5. Causes of Depression • Genetic predisposition • Social learning factors • Tendency to react negatively toward stress • Serious loss or other unwelcome life-altering event ALL EVENTUALLY LEAD TO A CHEMICAL IMBALANCE IN THE BRAIN.

  6. Chemical Imbalance • Deals with three principle monoamines (neurotransmitters): • dopamine • norepinephrine (noradrenalin) • serotonin (5-HT) • Abnormal levels create mood disturbance • Sometimes results from enzyme-substrate interactions • More frequently from abnormal reuptake during monoamine catabolism

  7. Monoamine Oxidase • Monoamine oxidase (MAO) is the enzyme ultimately responsible for the catabolism of the neurotransmitter into its respective metabolites

  8. Catechol-O-methytransferase • Abbreviated COMT • Other party involved in the catabolism of monoamine • Provides alternate pathway forming different metabolites than if compound went straight through MAO • Follows same typical enzyme-substrate interaction • Even if monoamine goes through COMT, it will also undergo further breakdown by MAO

  9. Catabolism of Norepinephrine CH30 HO COMT OH OH HO CHCH2NH2 HO CHCH2NH2 MAO MAO HO CH30 OH OH HO CH CHO HO CH CHO ALRED ALRED ALDH ALDH HO HO CH30 CH30 OH OH OH OH HO CHCOOH HO CHCH2OH HO CHCH2OH HO CHCOOH DHMA DHPG MHPG VMA

  10. Catabolism of Dopamine CHCH2NH2 CH2CH2NH2 COMT H3CO OH OH OH MAO MAO CH2CHO CH2CHO CH CHO OH OH H3CO OH ALDH ALRED ALDH ALRED CH2COOH CH2CH2OH CH2COOH CH2CH2OH OH OH OH OH H3CO OH H3CO OH DOPAC HVA

  11. Catabolism of Serotonin HO CH2 CH2 NH2 NH MAO HO CH2 CHO NH ALDH ALRED HO HO CH2 COOH CH2 CH20H NH NH 5-HIAA

  12. Metabolites • The metabolites formed during the breakdown of each neurotransmitter enable physicians to determine the effectiveness of medications. • DHMA and MHPG are the primary metabolites of norepinephrine and are measured most frequently. • HVA and DOPAC are dopamine’s main metabolites. • Serotonin’s predominant metabolite is 5-HIAA. • Metabolites can be obtained through cerebrospinal fluid, blood plasma, saliva, and urine. • Conjunctive measures help determine specific enzymatic abnormalities.

  13. Psychopharmacology • The study of the actions of drugs on the mind (Webster’s) • Study of drugs that affect thinking, feeling, and action, emphasizing those drugs that affect abnormalities in thought, affect, and behavior (AccessScience) • Concerned with four major classes of drugs linked to four major psychiatric disorders: anxiety, depression, mania, and schizophrenia

  14. SSRI • Selective Serotonin Reuptake Inhibitor • Ex: Zoloft (sertraline hydrochloride) • (cis-1S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-napthalenamine hydrochloride

  15. SSNRI • Selective Serotonin and Norepinephrine Reuptake Inhibitor • Ex: Cymbalta (duloxetine hydrochloride) • (+)-(S)-N-methyl-γ-(1-naphthyloxy)-2-thiophenepropylamine hydrochloride

  16. TCA • Tricyclic antidepressant • Ex: Tofranil (imipramine hydrochloride) • 5-[3-(dimethylamino)propyl]-10,11-dihydro-5H-dibenz [b,f]azepine monohydrochloride

  17. MAOI • Monoamine Oxidase Inhibitor • Ex: Aurorix (moclobebide) • p-chloro-N-(2-morpholinoethyl) benzamide

  18. Conclusions • These are the four most commonly prescribed classes of antidepressants • We know that there is some action involved, but there is never 100% proof that antidepressants offer long-term effects on depression • Therefore, we can only say that antidepressants alleviate the symptoms, not the disorder • Depression is not a character flaw or caused by bad parenting as some might believe • It is a chemical imbalance that has high rates of response to pharmacological intervention