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Biochemistry of Depression and Commonly Prescribed Antidepressants. Tricia Hill Biochemistry 7 December 2006. Purpose of Research. Recent issues regarding increased use of antidepressants Concern about long-term effects of antidepressants Previous rise in U.S. suicide rates

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biochemistry of depression and commonly prescribed antidepressants

Biochemistry of Depression and Commonly Prescribed Antidepressants

Tricia Hill

Biochemistry

7 December 2006

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purpose of research
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

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depression
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

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causes of depression
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.

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chemical imbalance
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

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

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catechol o methytransferase
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

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catabolism of norepinephrine
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

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catabolism of dopamine
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

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catabolism of serotonin
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

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metabolites
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.

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psychopharmacology
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

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slide13
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

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

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slide15
TCA
  • Tricyclic antidepressant
  • Ex: Tofranil (imipramine hydrochloride)
  • 5-[3-(dimethylamino)propyl]-10,11-dihydro-5H-dibenz [b,f]azepine monohydrochloride

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slide16
MAOI
  • Monoamine Oxidase Inhibitor
  • Ex: Aurorix (moclobebide)
  • p-chloro-N-(2-morpholinoethyl) benzamide

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conclusions
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

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