L49. Dopamine Drugs

L-Dopa

Carbidopa - used in adjunct with L-Dopa to prevent the conversion of L-Dopa to DA early in the periphery. Carbidopa is the gatekeeper of L-Dopa ensuring the drug gets to the CNS without being converted so that there in the brain it can then become DA

COMT inhibitor --> inhibits the breakdown of L-Dopa in the periphery since COMT likes to break down L-Dopa before the poor drug reaches the CNS and converts into DA. Thus, Entacapone is used as an adjunct with L-Dopa to ensure effectiveness

Selegine is an MAO inhibitor - it works by inhibiting the breakdown of residual DA from the CNS thus ensuring DA stays in the CNS a while --> used as adjunct

D2R/D3R agonists (ropinirole and pramipexole)

Weak partial D2R agonist - antipsychotic

Quetiapine Aripiprazole Risperidone

In addition to being D2R antagonists (block dopamine's activity), they interact with other monoamine receptors like 5HT2A

Tyrosine hydroxylase

Tyrosine (Tyrosine Hydroxylase) --> DOPA (Aromatic Amino Acid Hydroxylase) --> Dopamine

Excitatory - INC cAMP, INC PIP2

Inhibitory - DEC cAMP, INC K+, DEC Ca+

Substantia Nigra and Adjacent Ventral Segmental Area

Directly activate DA receptors in the CNS --> trick the brain into thinking there's DA even though there isn't (the receptor is getting activated and the effects of DA is being mimicked but there isn't an actual increase in DA levels)

Monoamine receptors and D2R

1. Enter pre-synaptic neuron via DAT
2. Amphetamines (AMP) inhibit MAO (which typically break down DA) = DA levels say high in the vesicles
3. AMP Enters vesicles via VMAT2 --> moves dopamine from the vesicles and out into the cytoplasm
4. Newly displaced dopamine gets pushed out of the neurons via REVERSE DAT (mediated by the AMP)

Blocks DAT = DA doesn't get taken up into the neuron and it stays in the synaptic cleft for longer