Intro to CNS pharmacology 2 Flashcards
what are the 2 types of cholinergic receptors?
1- nicotinic
2- muscarinic
nicotinic receptors are part which types of receptors?
ionotropic (cholinergic)
where are nicotinic receptors mostly found?
- mostly skeletal muscle
- some in the CNS
muscarinic receptors are part of which types of receptors?
metabotropic (cholinergic)
where are muscarinic receptors found?
mostly in the CNS
Acetylcholine is synthesized from what, and by which enzyme?
synthesized from choline and acetyl-CoA.
By choline acetyl transferase (CAT).
what is the rate limiting step in acetylcholine synthesis?
choline uptake
in acetylcholine’s nicotinic effects the signal is terminated by what?
acetylcholine esterase and possibly an uptake mechanism.
acetylcholine’s nicotinic effects are linked to which type of diseases?
neurodegenerative diseases (eg. Parkinson’s, Alzheimer’s)
Loss of cholinergic neurons at the basal forebrain are a pathologic feature of which disease?
alzheimer’s
which anticholinesterase drugs provide benefit to AD patients, and how do they work?
Tacrine and donepezil, they work by reducing Ach degradation.
muscarinic receptor effect speed compared to nicotinic effects is… (faster or slower)?
slower effects
Acetylcholine muscarinic effects is responsible for mediating which behavioral effects of Ach?
Arousal.
Learning.
and short-term memory
biogenic amines is derived from what?
amino acids.
catecholamine are derived from which amino acid?
Tyrosine
give examples of catecholamine?
-Dopamine.
-Norepinephrine (noradrenaline).
-Epinephrine (adrenaline).
Norepinephrine and epinephrine binds to which type of receptor?
adrenergic receptors.
speed of response of NE and E at adrenergic receptors?
slow responses
What is the category of dopamine?
biogenic amine.
what is the postsynaptic effect of dopamine?
Excitatory or inhibitory.
dopamine receptors are bound by which type of drugs?
antipsychotic drugs
what are the 4 dopaminergic pathways in the CNS?
1-meso-limbic.
2-nigro-striatal.
3-hypothalamus.
4- Chemoreceptor trigger zone (CTZ).
What is the importance of the dopaminergic meso-limbic pathway? which disease is related to it?
important in emotion an reward pathway.
related to schizophrenia.
What is the importance of the dopaminergic nigro-striatal pathway? which disease is related to it?
important in motor control.
related to Parkinson’s disease.
What is the importance of the dopaminergic hypothalamus pathway?
important in some hormone regulation (eg. prolactin).
What is the effect of the dopaminergic Chemoreceptor trigger zone pathway?
emetic effect “vomiting”
what are the 5 subtypes for DA receptors?
D1
D2
D3
D4
D5
Which DA receptor is responsible for Parkinson’s like effect, motor side effect, and extrapyramidal symptoms (EPS)?
D1 (including D5)
which DA receptor subtype gets blocked by antipsychotic drugs?
D2 (Including D3 and D4)
which DA receptor subtype gets blocked by haloperidol and clozapine?
they are antipsychotic drugs.
so they block D2 (including D3 and D4)
which type of nerves is norepinephrine released form?
adrenergic nerves.
norepinephrine is formed from which catecholamine?
dopamine
what are norepinephrine receptors?
Alpha 1 and 2
Beta 1 and 2
which organ is epinephrine released from?
adrenal glands.
epinephrine is synthesized from which catecolamine?
norepinephrine
inhibition of noradrenaline happens through the activation of which receptor?
activation of beta receptors.
excitation of noradrenaline happens through the activation of which receptors?
activation of both alpha and beta receptors.
noradrenergic pathways are important in what?
1- arousal.
2- control of blood pressure.
3- mood control.
what is venlafaxine (effexor)?
antidepressants.
how dose venlafaxine (effexor) work?
it is a serotonin norepinephrine reuptake inhibitors (SNRIs).
how does cocaine work?
reuptake inhibitors.
amphetamine is an example of a drug which is linked to which pathway?
noradrenergic pathways.
how does amphetamine effect the noradrenergic pathway?
increases catecholamine in the brain, increases wakefulness, alertness and exploratory activity.
what are clonidine and methyldopa?
centrally acting antihypertensives.
how do clonidine and methyldopa work?
they are agonists to alpha 2, couples to Gi protein, decrease sympathetic discharge from the CNS.
which biogenic amine blocks hunger and tiredness in the brain?
histamine.
what is the postsynaptic effect of histamine?
excitatory.
all histamine receptors are which type of receptors?
G-protein coupled.
what are the effects of histamine in the brain?
affects arousal and attention.
what are the effects of histamine in the peripheries?
inflammation and vasodilation.
what is the postsynaptic effects of serotonin?
excitatory.
what is the source of 5-hydroxytryptamine (5-HT) (serotonin)?
tryptophan
how does HT-5 affect the GIT?
Increases GIT motility.
how does HT-5 affect platelets?
platelet aggregation.
5-HT has which effect in the CTZ?
vomiting
what effects does 5-HT have on the CNS?
control of:
- appetite,
- sleep/wakefulness,
- mood and emotion,
- behaviors “hallucinations”,
- pain perception,
- vomiting.
antidepressants have which effects on appetite?
loss of appetite.
5-HT is involved in which clinical conditions?
- migraines.
- mood disorders and anxiety.
what type of drugs treat mood disorders and anxiety? “HINT: related to 5-HT”
tricyclic “TCA” and selective serotonin reuptake inhibitors “SSRI”
What type of receptors are serotonin receptors?
there are 14 distinct receptor subtypes, 13 are G protein coupled receptors (GPCRs), and one (5-HT3) ligand-gated ion channel (LGIC)
list serotonin effects? (HINT: there are 4)
1- involved in sleep/wakefulness cycle.
2- SSRI and depression and anxiety.
3- coagulation.
4- antiemetic effects.
name amino acid neurotransmitters at excitatory synapses?
glutamate and aspartate.
name amino acid neurotransmitters at inhibitory synapses?
GABA (gamma-amino butyric acid) and glycine.
what category is glutamate?
small molecule
what are glutamate neurons called?
glutaminergic neurons.
where is glutamate synthesized from?
glutamine from glia.
what are glutamate ionotropic receptors?
NMDA.
AMPA.
kainate
where is the location of NMDA ionotropic glutamate receptors?
late EPSP
which ionotropic glutamate receptor is glycine and mg+2 dependent?
NMDA
Where is the AMPA ionotropic glutamate receptor located?
Early EPSP
Where is the kainate ionotropic glutamate receptor located?
Early EPSP
what are the metabotropic glutamate receptors?
mammalian metabotropic glutamate receptors. are all named mGluR
the major EAA’s in the CNS are?
1- L-Glutamate (glutamic acid).
2- Aspartate.
what is the major excitatory transmitter in the CNS?
L-Glutamate.
what major excitatory transmitter is widely distributed in the CNS?
L-Glutamate.
what major inhibitory transmitter is widely distributed in the CNS?
GABA
what is the major inhibitory transmitter in the CNS?
GABA
GABA is synthesized mainly from what?
glutamate via GAD (Glutamic acid decarboxylase).
decarboxylases are vitamin ____ dependent enzymes.
B6
Vitamin B6 can lead to _____ due to not enough synthesis of GABA
seizures
glycine is mostly found where?
in the spinal cord.
strychnine antagonist causes what?
convulsions
which category is GABA from?
small molecule
which type of neuron is GABA?
GABAergic neurons.
what postsynaptic effect does GABA have?
inhibitory.
GABA is made from what?
glucose.
what is the ionotropic GABA receptor called?
GABA A
what is the metabotropic GABA receptor called?
GABA B
what does GABA A receptor do?
gates CL- channel
what does GABA B receptor do?
gates K+ channel
where is GABA A receptor located?
post-synaptically
GABA A opens for what?
Chloride.
GABA A chloride opening results in what?
decrease in membrane excitability (hyperpolarization).
list the drugs that interact in GABA A?
1- Benzodiazepine.
2-Convulsants.
3-Barbiturates.
what are the effects of benzodiazepines when they interact at GABA A?
reduction of anxiety, induction of sleep, muscle relaxant, and reduction of convulsion.
_________ are GABA A antagonist.
Convulsants.
give an example for barbiturates that interact at GABA A?
phenobarbital
GABA B is which type of receptor?
GPCR
what is the effect of GABA B?
inhibits cAMP production.
short chains of amino acids
neuropeptides.
give the 2 examples of neuropeptides, and where are they found.
- endogenous opiates (endorphins - in the brain)
- morphine - like (vasopressin - antidiuretic hormone - found in the posterior pituitary).
which purine is an NT?
ATP
what is the effect of the ionotropic ATP receptor?
Fast excitatory NT
what is the effect of the metabotropic ATP receptor?
neuromodulation
which type of purine is involved in neuronal toxicity?
ATP cytosol
list the effects of adenosine (A receptors)?
- sedative.
- anticonvulsant.
- neuroprotective.
- methylxanthines, (increase wakefulness).
give examples of methylxanthines?
caffeine and theophylline, which are A2 antagonists.
nitric oxide is synthesized by which enzyme?
nitric oxide synthase
____ increases NO production
CA +2
NO increases the production of ________
cGMP
excessive NO production causes what?
neurotoxicity.
NO is important in what?
- LTP — Memory.
- protect against ischemic brain damage.
list the 3 CNS barriers?
1- Blood - brain barrier.
2- Blood - CSF barrier.
3- the arachnoid barrier.
what is the favoured route for global delivery of drugs to all brain cells?
BBB
Which barrier is created at the level of cerebral capillary endothelial cells by tight junction formation?
BBB
what is the largest area for exchange to the brain in humans?
BBB
which CNS barrier is NOT an important route for the entry of solutes into brain?
arachnoid barrier.
which medical condition causes the BBB to be leaky
Bacterial meningitis.
what are the factors that influence drug entry through BBB? “hint: there are 7”
1- size.
2- molecular conformation.
3-lipophilicity.
4-charge.
5- enzymatic stability.
6- affinity to transporter.
7- plasma protein binding.
