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Neurotransmitters: Monoamines. Lesson 9. CRITERIA. 1. NT found in axon terminals 2. NT released by action potentials 3. Synthesis identified 4. External application mimic normal response 5. Pharmacology same for normal and externally applied NT

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criteria
CRITERIA

1. NT found in axon terminals

2. NT released by action potentials

3. Synthesis identified

4. External application mimic normal response

5. Pharmacology same for normal and externally applied NT

  • Mechanism of action
  • Actions of agonists & antagonists
  • Direct & indirect ~
monoamines
Monoamines
  • Amino acid precursors
    • single amine group
  • 2 groups
    • Catecholamines - catechol ring
    • Indolamine - indole ring
  • Affected by many of same drugs ~
monoamines4
Catecholamines

Dopamine - DA

Dopaminergic

Norepinephrine - NE

Noradrenergic: neurons

Adrenergic: drugs/receptors

Epinephrine - E

Adrenergic ~

Indolamine

Serotonin - 5HT

Serotonergic

Monoamines
monoamines5
Monoamines
  • Terminated by...
    • reuptake
    • MAO - monoamine oxidase
    • COMT - catechol-O-methyltransferase
    • also in liver
  • Reserpine  blocks storage
    • initially stimulates NT release
    • profound depletion over several days ~
indirect monoamine agonists
Indirect Monoamine Agonists
  • MAOI
    • monoamine oxidase inhibitors
  • Reuptake blockers
    • Tricyclic antidepressants
      • aka Non-selective reuptake inhibitors
    • Cocaine & Amphetamine ~
slide7

Reserpine

MAO

MAO

Monoamines

A

COMT

dopamine
Dopamine
  • Only in central nervous system
    • mostly inhibitory systems
    • all metabotropic
  • Reward
  • Schizophrenia
  • Movement
    • Nigrostriatal Pathway
  • At least 5 DA-R types: D1, D2, etc. ~
dopaminergic drugs
Dopaminergic Drugs
  • Agonist
    • L-DOPA
  • Antagonists
    • Chlorpromazine
      • D1
    • Haloperidol
      • D2 ~
dopamine synthesis

tyrosine

hydroxylase

aromatic amino acid

decarboxylase

DOPA

DA

Dopamine Synthesis

Tyrosine

DOPA

decarboxylase

  • AADC (aromatic amino acid decarboxilase) is AKA DOPA decarboxilase ~
norepinephrine
Norepinephrine
  • Peripheral N.S.
    • Sympathetic neuroeffector junction
    • Adrenal glands
  • Central N.S.
    • Hypothalamus
    • Locus coeruleus
  • a & b groups of receptor subtypes
    • metabotropic ~
adrenergic drugs
Adrenergic Drugs
  • Agonists
    • Mescaline
    • Ephedrine
    • Clonidine
  • Antagonist
    • Yohimbine (a2)
    • Propranalol (b-blocker) ~
slide13

tyrosine

hydroxylase

dopamine

b hydroxylase

DOPA

DA

NE

Norepinephrine Synthesis

AADC

Tyrosine

serotonin
Serotonin
  • NOT a catecholamine
  • Peripheral
    • 98% in blood & smooth muscle
  • Central N.S.
    • Raphe nucleus
    • Hypothalamus
  • R subtypes: 5HT1 , 5HT2 , etc. ~
serotonergic drugs
Serotonergic Drugs
  • Agonists
    • SSRIs
      • Selective Serotonin Reuptake Inhibitors
    • MDMA
      • Ecstasy
      • neurotoxicity in rats & primates ~
serotonergic drugs16
Serotonergic Drugs
  • Antagonists
    • Psilocybin
    • LSD
      • autoreceptor agonist in CNS
    • Buspirone
      • 5HT1a
  • Inverse agonist
    • ketanserin ~
serotonin synthesis

tryptophan

hydroxylase

AAADC

5-HT

5-HTP

Serotonin Synthesis
  • 5-HTP – 5 hydroxytryptophan
  • 5-HT – 5 hydroxytryptamine

Tryptophan