2-3: CNS Stimulants

what are the 8 common neurotrasmitters?

1. acetylcholine

2. norepinephrine

3. epinephrine

4. dopamine

5. seretonin

6. y-aminobutyric acid (GABA)

7. histamine

8. glutamate

acetylcholine

if R = H —> Norepinephrine (aka NE, Noradrenaline)

if R = CH3 —> Epinephrine (aka E, adrenaline)

dopamine

histamine

seretonin

y-Aminobutyric Acid (GABA)

Glutamate

what are the two therapeutic uses of CNS stimulants?

Central Sympathomimetic Agents and Antidepressants

Methylxanthine Alkoids:

• What are the 3 MOA?

• which is the most important?

moa:

1. competitively binds to adenosine (adenosine is CNS depressant) - most important!

2. inhibit phosphodiesterase —> increases cAMP

3. alter calcium distribution (increase)

what are the 3 uses of Methylxanthine Alkoids?

1. bronchial asthma

2. infant apnea

3. migraine headaches

There are many CNS stimulants that are derivatives of Xanthine

which amines are acidic?

which amines are weakly basic?

is the functional group in pink acidic or no?

acidic amines = green

weakly basic amines = blue

functional group is NOT acidic

the conjugate acid of caffeine (right) has pka of ____

0.6

which methylxanthine is this? (3 methyls added to xanthine)

what is its moa?

what is the pka of its conjugate acid shown in the picture?

caffeine

1. inhibit adenosine

2. inhibit PDE (increase cAMP)

3. increase calcium

pka = 0.6

which methylxanthine is this? (2 methyls added onto the ring)

what is its moa?

what is its pka?

theophyline

moa:

1. inhibit adenosine

2. inhibit PDE (increase cAMP)

3. increase Ca2+

pka = 9

which methylxanthine is this? (methyl added onto imidazole and the bottom of ring)

what is its moa?

what is its pka?

theobromine

moa

1. inhibit adenosine

2. inhibit PDE (increase cAMP)

3. increase Ca2+

pka = 7.89

do methylxanthines have low or high water solubility (think of caffeine!)

how does impact how the drug is taken?

LOW - which is why caffeine is served hot to increase solubiity

decreases oral bioavailability and ability to be infused

how can you increase water solubility of methylxanthines so they can be used for oral usage and iv infusions?

salt formation: adjust acditiy or basicity of solvent to create salts that will disolve better in H20

add substituents such as OH that will react with water

what is caffiene used for?

what is theophyline used for?

which is which?

top = caffeine = infant apnea and migraine headaches

bottom = theophyline = bronchial asthma

what are the three methylxanthine CNS stimulants derived from Xanthine?

1. caffeine

2. theophyline

3. theobromine