Adrenergic transmission and presynaptic modification Flashcards
Epinephrine and NE synthesis
- Tyrosine → DOPA (dihydroxyphenylalanine) via Tyrosine Hydroxylase. Rate limiting step.
- DOPA → dopamine (DA)
DOPA decarboxylase - Transported into vesicle via VMAT
- Dopamine → NE
Dopamine beta hydroxylase, within vesicle. - NE → Epinephrine
PNMT
Presynaptic adrenergic inhibitors
Metyrosine -inhibits TH
Carbidopa and Benserazide - inhibit DOPA decarboxylase
Reserpine - inhibits VMAT and causes presynaptic depletion of monoamines NE, 5HT, DA, effects very long lasting, weeks.
Guanethidine, Debrisoquine, Bretylium - Displace NE from the vesicles causing vesicular NE depletion.
Alpha 2 agonists: - Clonidine - Alpha-methyl-dopa. Converted to alpha-methyl-NE the active drug - Guanfacine For ADHD - Guanabenz For hypertension Dexmedetomidine anxiolytic
Imidazoline 1 receptor agonists (are also alpha 2 agonists)
All the different Adrenergic reuptake inhibitors, presynaptic potentiators.
(11 drug classes)
1) L-DOPA, increased available precursor.
2) monoamine releasers Tyramine Ephedrine Pseudoephedrine Amphetamine Methamphetamine Methylphenidate (ritalin)
3) Reuptake inhibitors:
Cocaine, Amphetamine, Dextroamphetamine, Methylphenidate
4) Atypical antidepressants.
Buproprion and Trazodone –> inhibit NET
Mirtazepine –> increases presyaptic release
5) nonselective MOA inhibitors,
Tranylcypromine
Phenelezine
Isocarboxazide
6) MOA-B inhibitors.
Selegeline
Rasageline
Safinamide
7) RIMAs
Moclobemide
8) TCAs Amytryptiline - Nortryptyline Imipramine - Desipramine Clomipramine Trimipramine Doxepin
9) SNRIs: Venlafaxine Desvenlafaxine Duloxetine Milnacipram, Levomilnacipram
10) ADHD drugs:
Atomexitine - inhibits NET
Methylphenidate - ritalin, inhibits NET and DAT
11) alpha 2 antagonists
Mirtazapine - atypical antidepressant
Yohimbine - not used clinically
Imidazoline 1 receptor agonists
Moxonidine
Rilmenidine
Bind these receptors in the medulla.
Decrease sympathetic tone, for hypertension, also alpha 2 agonists.
BUT only if given orally, if given IV it can have direct peripheral effects and cause hypertension.
Side effects are parasympatholytic/antimuscarinic. Dry eyes, mouth, constipation, sedation.