Neurotransmitter & Drugs 2

Question 1

what is the order of synthesis of the catecholamines?

Answer 1

tyrosine is converted by tyrosine hydroxylase (rate-limiting step) into DOPA –> dopamine –> norepinephrine –> epinephrine

Question 2

what does the termination of action of dopamine look like?

Answer 2

either:
- reuptake via DAT (Na+/DA symporter) and repackaging
- reuptake and degradation in the terminal: by monoamine oxidase (MAO) into DOPAC or by COMT into HVA
- degradation in the synaptic cleft by COMT

Question 3

where are the cell bodies of dopamine neurons located and what type of dopamine receptors are there?

Answer 3

cell bodies are located in the substantia nigra and the ventral tagmental area (VTA), dopamine neurons are all metabotropic but can be D1: D1 and D5 (Gs) or D2: D2, 3, and 4 (Gi/o)

Question 4

what are some drugs that act on dopamine?

Answer 4

levodopa enhances dopamine synthesis via precursor loading, given with carbidopa
resperine is a neuroleptic that blocks VMAT so that dopamine cannot be packaged and therefore is degraded by COMT

Question 5

what is cocaines mechanism of action?

Answer 5

cocaine in an indirect monoamine agonist that binds to dopamine reuptake receptors and blocks them so that dopamine cannot be taken up, the dopamine stuck in the cleft then overstimulates the receptors so that when cocaine wears off the receptors are less active leading to craving and withdrawal

Question 6

what is amphetamines mechanism of action?

Answer 6

amphetamines are indirect monoamine agonists that cause changes in the protein structure of dopamine reuptake receptors that causes dopamine to move in the opposite direction and be released into the synapse, more dopamine then enters cleft and its reuptake remains blocked

Question 7

what is caffeine’s mechanism of action?

Answer 7

caffeine blocks the inhibitory effects of adenosine (adenosine indirect agonist) on glutamate and dopamine release in the CNS by turning the Gi receptors to Gs which increases adenylyl cyclase

Question 8

where are norepinephrine cell bodies and terminals located in the brain?

Answer 8

93% of cell bodies are located in the locus coeruleus and the lateral tagemental nucleus (LTN), 7% of the adrenal medulla is norepinephrine, terminals span the entire brain

Question 9

what is the termination of action of norepinephrine?

Answer 9

either:
- reuptake via NET and repackaging
- reuptake and degradation by MAO into DHMA/DHPG or COMT into VMA/MHPG
- degradation by COMT in the presynaptic cleft

Question 10

how is epinephrine synthesized?

Answer 10

tyrosine is converted into norepinephrine, PNMT in the cytoplasm then converts norepinephrine into epinephrine

Question 11

where are epinephrine cell bodies located in the brain?

Answer 11

90% of cell bodies are in the adrenal medulla and 10% are in the lateral tegmental area in the brain stem, 90% of the adrenal medulla is epinephrine

Question 12

what is the termination of action of epinephrine?

Answer 12

reuptake by NET and repackaging, reuptake and degradation by MAO/COMT in the presynaptic terminal into HVA

Question 13

what are the different types of adrenergic receptors?

Answer 13

all adrenergic receptors are metabotropic and mostly excitatory, a1 receptors are Gq and move K+ into cell, a2 receptors are Gi and move K+ out of the cell, B receptors are Gs or Gi

Question 14

what are some drugs that act on adrenergic receptors?

Answer 14

albuterol is a B2 agonist that causes bronchial dilation
propranolol is a B2 direct antagonist used to treat PTSD and anxiety, reduces freezing behavior to cue induced fear

Question 15

why can adrenergic neurons release dopamine?

Answer 15

because NE and E are made from dopamine so dopamine that hasn’t been converted yet can be released