Duration of β₁ antagonists

Ester: shortest acting

Amide: Intermediate acting

Ether: longest acting

Tricyclic antidepressents

2° amine:

3° amine:

2° amine: NE uptake blocker

3° amine: 5HT uptake blocker

Cocaine

blocks reuptake of NE & DA

• Activates adenylate cyclase
• ↑cAMP

• Pre & post synaptic
• Inhibit adenylate cyclase
• ↓cAMP

• Same side
• D₁ = D₂

• Opposite side
• D₂ > D₁

(+SAM)

OH -> OCH₃

(+NAD)

Aldehyde -> Carboxylic acid

How do D₂ autoreceptors inhibit DA?

• Inhibit synthesis (Tyrosine hydroxylase)
• Inhibit release

• Substantia Nigra origin of corpus striatum)
• controls posture, muscle tone, movement
• Lack = Parkinson's, EPS.
• (ACH works with DA for balance)

• Behavior & Emotion
• Too much: Schizophrenia (Psychosis)
• Too few: Depression

• Anterior pituitary
• DA decreases prolactin release

• DA controls locomotion

• ↑ DA release
• ↓ DA uptake

Taken up actively by presynaptic neurons

(Parkinsin's)

• Mimics GABA
• CNS suppression (↓ DA)

• Primary: Parkinson's
• secondary: RLS (Requip/Mirapex)

DA agonist

NOTE:

1. Aromatic ring
2. Basic N (separated from AR by 2 atoms)
3. Minimal bulk
4. α rotomeric

• Primary: Antipsychotics
• Minor: Anti-emetic (Metoclopramide)
• Adjuvent: Depression/Bipolar

Phenothiazine

NOTE

• S
• separation of 2-4 between AR and N
• Cl = EWG = required.

Phenothiazine

Preferd activity

Tyrosine Hydroxylase inhibitor

NOTE:

• Extra methyl group prevents enzyme from acting (reversible inhibition)

Treat pheochromocytoma (excess NE/E)

LAAAAD inhibitor

NOTE:

• Extra methyl group.  converted by LAAAAD into a false NT
• Presynaptic α₂ agonist (↓ BP)

smooth muscle contraction

• Agonist:decongestion, vasoconstriction
• A₁ Antagonist: treat hypertension & BPH
• A₂ Antagonist: treat depression

Phenethanolamine

NOTE:

OH

2-arylImidazoline

NOTE:

C

α₁ agonist

Phenethylamine (Amphetamine)

NOTE:

no OH

Indirect acting α₁ agonist (promote NE release)

2-aminoimidazoline (Clonidine)

NOTE:

ortho N, Halogen,

α₂ agonist

CNS antihypertensives. 

Imidazole based α₂ agonist

NOTE:

benzene substituants are O & M

Imidazoline

NOTE:

No halogen

α antagonist

β-Haloalkylamine

α2 antagonist irreversible

NOTE:

ether

Quinazoline (Doxazosin, longest acting)

α₁ antagonist

Dobutamine

β1 (α₁ cancels out)