Chapter 6
How do SSRIs work?
block reuptake of serotonin
What are the three types of catecholamines present in the brain? What is the common precursor? What is the rate-limiting step and enzyme for this pathway?
dopamine, epinephrine, and norepinephrine. Common Precursor: Tyrosine Rate limit: Conversion of Tyrosine to DOPA via Tyrosine Hydroxylase
What are two proteins important in the breakdown of catecholamines? Where are they located?
monoamine oxidase (MAO): catabolism in pre-synaptic mitochondria. Phenelzine can inhibit MAO which functions as an antidepressant Catechol-o-methyltransferase (COMT): catabolism in post-synaptic cytoplasm. Val154Met is a gene substitution which is associated with Schizophrenia (leading to slow COMT activity)
What are the two major acetylcholine receptors?
muscarinic and nicotinic
Where is histamine synthesized?
posterior hypothalamus
What are two methods for inactivating catecholamine action?
reuptake to presynaptic terminal or enzymatic degradation
How is histamine synthesized?
synthesized from histidine via histidine decarboxylase
How is acetylcholine synthesized? What enzyme catalyzes the reaction?
-in cytoplasm -from acetyl-CoA and choline -catalyzed by *choline acetyltransferase (ChAT)*
What are the 3 major dopaminergic projections in the CNS? What are physiological relationships with each projection?
1. Mesostriatal- locomotor regulation 2. Mesoaccumbens/mesocortical: cognitive and reward 3. Tuberinfundibular: pituitary regulation and prolactin synthesis
Persticedes and insecticides are inhibitors for what type of neurotransmitter? what symptoms do they cause?
Acetylcholine transporters. Cause respiratory and muscle paralysis
Where is acetylcholine synthesized?
Basal Forebrain and pontomesencephalon
What is the action of norepinephrine transporters (NET)? What is a class of inhibitors that affect the NET?
Binds to norepinephrine (and dopamine) and transport it into pre-synaptic terminal for re-use or degradation. Tricyclic anti-depressants (TCA) inhibit NET thus increasing the level of DA and NE in the brain
What are drugs that affect the cholinergic synapse?
Botulinin tetanus alpha-latrotoxin Curare Atropine
What kind of receptors are targets for antipsychotics?
D2R
What enzyme breaks down DOPA to Dopamine?
DOPA decarboxylase
What is the action of the dopamine transporter? What is an inhibitor for this transporter?
Dopamine transporters bind dopamine and transport it back into pre-synaptic terminal for re-use or degradation. Cocaine can inhibit DAT thus increasing dopamine in the synaptic cleft. Amphetamines increase release dopamine via DAT (there is a reverse transport)
What drug is often given to patients with Parkinson's Disease? Why?
L-DOPA. It is an oral pro-drug that allows first pass metabolism in the liver to break down the L-DOPA into dopamine, which can then use the enteric nervous system to travel to dopaminergic neurons and release dopamine.
What drugs regulate levels of Tyrosine hydroxylase (TH)?
Nicotine and caffeine
What are the main functions of Norepinephrine? Where is it synthesized? What disorders is it involved in?
Regulates sleep-wake cycle, attention, arousal, and anxiety. Synthesized in the Locus Ceruleus. Inolved in PTSD and ADHD
What are drugs that affect the noradrenergic synapse?
Reserpine, SNRI, Propanolol, MAOI
What are 4 drugs that inhibit serotonergic synapses?
Reserpine, SSRI and SNRI, MAOI, and antipsychotics
What are common drugs that affect the dopaminergic pathway?
Reserpine, cocaine, amphetamines, antipsychotics
What are the effect of ecstasy and MDMA on serotoning transporters?
Reverse transporter function, thus increase 5HT levels in synapse
What is the synthetic pathway for Serotonin?
Tryptophan -(Tryptophan-5-hydroxylase [TPH])-> 5-hydroxytryptophan -(Aromatic L-amino acid decarboxylase)-> Serotonin (5-hydroxytryptamine)
What is the biosynthetic pathway for epinephrine synthesis?
Tyrosine broken down by TH to DOPA. DOPA is broken down by DOPA decarboxylase to make Dopamine. Dopamine can be broken down by Dopamine-Beta-hydroxylase to norepinephrine. Norepinephrine can then be broken down by phenylethanolamine N-methyltransferase (PNMT) to epinephrine.
What vesicular transporter is reponsible for the transport and storage of serotonin?
VMAT (vesicular monoamine transporter)
How are catecholamines stored? What other molecules are transporter/stored? What is an inhibitor for this transporter?
Vesicular monoamine transporter (VMAT). Can also store serotonin, transport other amines such as amphetamines. Inhibited by Reserpine thus decreasing storage levels
Where is PNMT enzyme located in the brain?
adrenal medulla and brainstem