Neuropharmacology Flashcards
What do the nervous system and endocrine system do?
coordinate the regulation and integration of body functions
Endocrine system
various levels of blood-borne hormones
nervous system
transfer signals via the transmission of electrical impulses over nerve fibers to effector cells, which release neuromodulator substances
Central Nervous System
brain and spinal cord
Peripheral Nervous System
neurons located outside the brain and spinal cord
efferent nervous system
efferent neurons deliver signals away from the CNS to the peripheral tissues
autonomic nervous system and somatic nervous system
Afferent nervous system
afferent neurons deliver signals from the peripheral tissues to the CNS
provide sensory info to regulate the function of the efferent division through neural pathways
Somatic Nervous System
voluntary functions
contraction of skeletal muscles, essential for locomotion
Autonomic nervous system
involuntary functions
vital bodily functions without consciousness
require sensory input from peripheral structures to provide information on the current state of the body
includes the sympathetic nervous system, the parasympathetic nervous system, and the enteric nervous system
ganglion
collection of neuron cell bodies in the PNS
functions for communication
Where are preganglionic neurons located
in the CNS
Where are postganglionic neurons located?
distal/posterior to a ganglion
Functions of the sympathetic nervous system
adjust to stressful situations
incr heart rate and blood pressure
incr blood flow to skeletal muscles and the heart
divert flow from the skin and internal organs
dilate pupils and bronchioles
Functions of parasympathetic nervous system
maintain homeostasis within the body, essential bodily functions
opposes/balances the actions of the sympathetic division
Sympathetic has wide distribution and parasympathetic has x
short distribution
Hormones
endocrine cells secrete hormones into the circulation, traveling throughout the body, initiating effects on target cells
Local mediators
cells secrete chemicals that act on nearby cells
rapidly destroyed, don’t enter circulation
Neurotransmitters
communications between nerve cells occurs via chemical signals released from the nerve terminals
triggered by arrival of action potential at the nerve ending
How are neurotransmitters signals mediated?
by binding to receptors on the cell surface of target organs
Types of neurotransmitters in the autonomic nervous systems
ACh
NE
Epi
Sympathetic innervation of adrenal medulla
preganglionic neuron releases ACh
it binds to nicotinic receptor on adrenal medulla
Epi and NE released into blood
they bind to adrenergic receptor
Sympathetic path
preganglionic neuron releases ACh
it binds to the nicotinic receptor
postganglioni neuron releases NE
NE binds to adrenergic receptor
parasympathetic path
preganglionic neuron releases ACh
binds to nicotinic receptor
postganglionic neurons release ACh
binds to muscarinic receptor
M1, M3, M5
stimulators of muscarinic receptors in parasympathetic nervous system
Gq-PLC-IP3/ DAG- Ca^2+
M2, M4
inhibitory muscarinic receptors in parasympathetic nervous system
inhibits adenylyl cyclase and regulates specific ion channels
Synthesis and Release of ACh from cholinergic neuron
- Ach is made
- taken up into storage vesicles
- released in to synaptic cleft
- binds to nAChR
- AChE degrades ACh
- Choline is take back up by the neuron
muscarinic receptors
cholinoceptors
weak affinity for nicotine
GPCR
nicotinic receptor
cholinoceptors
weak affinity for muscadine
iontropic receptor
What does ACh do to the cardiovascular system?
vasodilation
decr heart rate, cardiac conduction velocity in AV-node, and force of contraction
effects mediated by M2 receptors:
incr K^+ current
decr L type Ca^2+ current
decr cAMP
inhibition of NE release form sympathetic nerve terminals
What does ACh do to the respiratory tract?
bronchoconstriction
increased tracheobronchial secretion
effects mediated by activation of M3 receptors
What does ACh do to the urinary tract?
detrusor muscle contraction
incr urinary voiding pressure
ureteral peristalsis
effects mediated by M2 and M3 receptors
What does ACh do to the GI tract?
incr tone of GI muscle, muscle contraction, secretory activity of stomach and intestine
effects mediated by M2 and M3 receptors
What secretory and ocular effects is ACh responsible for?
glandular secretion
mitosis
effects mediated by M1 and M3 receptors
What effects does ACh have on the CNS?
cognition
motor control
appetite regulation
nociception
arousal
effects mediated by all 5 muscarinic receptors
Acetylcholine
muscarinic agonist
direct acting
used topically to induce miosis during eye exams or ophthalmic surgery
ganglionic blocker - arousal and cognitive enhancement
Methacholine
muscarinic agonist
used as an inhalant to diagnose bronchial airway hypersensitivity in patients with subclinical asthma
Bethanechol
muscarinic agonist
directs acting
used for treating urinary retention & inadequate emptying of bladder postoperatively
used to stimulate GI tract peristalsis and increase LES pressure
Pilocarpine
muscarinic agonist
direct acting
used to treat xerostomia following head and neck irradiation and Sjogren syndrome
used topically to treat glaucoma and as a miotic agent
reduces intraocular pressure in open and narrow angle glaucomas
uncharged tertiary amine that can penetrate the CNS
Contraindications of Muscarinc Agonists
asthma
COPD
urinary/GI obstruction
acid-peptic disease
cardiovascular disease
hypotension
hyperthyroidism
Adverse Effects of Muscarinic Receptor Agonists
Diaphoresis
NVD, abdominal cramps
blurry vision
hypotension
Muscarinic Receptor Antagonists
Prevents effects of ACh by binding to muscarinic receptors
little effect on nicotinic receptors
Ipatropium [Atrovent]
muscarinic receptor antagonist
used in respiratory tract to treat COPD, frequently in combo with inhaled long-acting beta 2 adrenergic receptor agonists
Tiotropium [Spriva]
muscarinic receptor antagonist
derivative of atropine, bronchodilator
used in respiratory tract to treat COPD, frequently in combo with inhaled long-acting beta 2 adrenergic receptor agonists
Oxybutynin [Ditropan]
muscarinic antagonist
used in the genitourinary tract to treat overactive bladder; relaxes detrusor muscle of the bladder
synthetic atropine-like drug
adverse effects: xerostomia, blurred vision, constipation and dyspepsia, drowsiness and confusion
Atropine
muscarinic antagonist
binds competitively and prevents ACh from binding to muscarinic receptors
used in GI tract to treat irritable bowl and increased tone, and to decrease GI motility
used in the cardiovascular system to reduce the degree AV-block that results from overactive parasympathetic tone
used in anesthesia to block vagaries responses to surgical manipulation of visceral organs
used to treat
- AChE poisoning from use of pesticides and nerve gas agents
- Spastic disorders of the GI tract
- organophosphate poisoning
- suppress respiratory secretions prior to surgery
- bradycardia
Homatropine [Ispto Homatropine]
muscarinic antagonist
administered topically to the eye to induce mydriasis and cycloplegia
Scopolamine [Transderm Scop]
muscarinic antagonist
used for the CNS
admin as a transdermal patch prophylactically to treat motion sickness
peripheral effects similar to atropine
greater actions in the CNS and longer duration of action compare to atropine
adverse effects: dry mouth, drowsiness, blurred vision i
Benztropine Mesylate [Cogentin]
muscarinic antagonist
used for the CNS
used to treat extrapyramidal side effects of antipsychotic drugs
Contraindications of Antimuscarinic agents
urinary tract/ GI obstruction
Adverse effects of antimuscarinic agents
xerostomia
constipation
blurred vision
dyspepsia
cognitive impairment
AChE inhibitors
enhance cholinergic tone by selectively blocking AChE
acts at cholinergic neuroeffector junctions
There are no vascular adverse effects with AChE because there is not x on the muscarinic receptors on the endothelium of blood vessels
cholinergic nerve fibers
Categories of AChE inhibitors
Reversible inhibitors
carbamylatipm inhibitors
organophosphate inhibitors
What kind of binding do reversible AChE inhibitors have?
non-covalent
Donepezil [Aricept]
AChE reversible inhibitor
used to treat the symptoms of Alzheimer’s disease
has not been shown to reduce healthcare costs/delay institutionalization
can be used with memantine in moderate to severe disease
What kind of binding do carbamylatipm inhibitors have?
Immediate duration covalent binding (15-30 min)
Neostigmine [Prostigmin]
indirect acting reversible muscarinic agonist carbamylatipm AChE inhibitor
used to treat myasthenia gravis, urinary retention without blockage and paralytic ileus
prevents postoperative abdominal distention
used as an antidote for competitive neuromuscular blockers
has intermediate duration of action 0.5-2hrs
What kind of binding do organophosphate inhibitors have?
long duration covalent binding (hours-permanent)
Malathion, and insecticide, and sarin, a nerve gas, are both examples of?
organophosphate AChE inhibitors
What effects do AChE inhibitors have on the body?
eye- miosis
GI Tract- enhanced gastric contractions, increased secretion of gastric acid, increased activity of small and large bowel
increased glandular secretion
increased contraction of smooth muscle of bronchioles and ureters decreased cardiac output
bradycardia
What are the symptoms of AChE inhibitor overdose?
salivation
lacrimation
urination
defecation
Nicotine
nicotinic agonist
acts at the neuromuscular junction
in PNS - transited stimulation followed by depression of autonomic ganglia and neuromuscular junction leading to paralysis
in CNS- stimulation, weak analgesia, tremors leading to seizures at toxic doses, excitation of respiration, nausea and vomiting
used in smoking cessation
Varenicline [Chantex]
nicotinic agonist
acts at the neuromuscular junction
partial agonist at nicotinic receptor
used in smoking cessation
adverse effects: mood and behavior changes
Pancuronium [Pavulon]
competitive nicotinic receptor antagonist
induces muscle paralysis by blocking nicotinic receptors at the neuromuscular junction
used for muscle relaxation during general anesthesia
used in the lethal injection cocktail
Direct acting muscarinic agonists
acetylcholine
bethanechol
carbachol
pilocarpine
nicotine
Indirect acting reversible muscarinic agonist
edrophonium
physostigmine
neostigmine
pyridostigmine
ambenonium
donepezil
rivastigmine
galantamine
indirect acting irreversible muscarinic agents
ecothiphate
Which muscarinic agonist reactivates AChE?
pralidoxime
Antimuscarinic agents examples
atropine
ipratropium
tiotropium
tropicamide
cyclopentolate
benztropine
trihexyphenidyl
darifenacin
fesoterodine
oxybutynin
solifenacin
tolterodine
trospium chloride
Which muscarinic antagonist is a ganglionic blocker?
nicotine
What are the 2 types of neuromuscular blockers?
nondepolarizing and depolarizing
Adrenergic agonist direct acting agents
epinephrine
norepinephrine
isoproterenol
dopamine
fenoldopam
dobutamine
phenylephrine
clonidine
albuterol
terbutaline
salmeterol
formoterol
mirabegron
indirect acting adrenergic agonists
amphetamine
cocaine
mixed action adrenergic agonists
ephedrine
pseudoephedrine
adrenergic antagonists: alpha blockers
phenoxybenzamine
phentolamine
prazosin
terazosin
doxazosinn
tamsulosin
alfuzosin
Yohimbine
Adrenergic Antagonists: Beta blockers- nonselective
propranolol
nadolol
timolol
Adrenergic antagonists: beta 1 blockers- selective
acebutolol
atenolol
betaxolol
bisprolol
esmolol
metaprolol
nebivolol
adrenergic antagonists: beta blockers with partial agonist activity
acebutolol
pindolol
adrenergic antagonists: beta blockers- antagonists of both alpha and beta adrenoreceptors
labetalol
carvedilol
Which adrenergic antagonist affects neurotransmitter uptake or release?
reserpine
physostigmine
indirect acting reversible muscarinic agonist
increases intestinal and bladder motility
reverses CNS and cardia effects of tricyclic antidepressants
reverses CNS effects of Atropine
uncharged tertiary amine that can penetrate the CNS
Rivastigmine
indirect acting reversible muscarinic agonist
first line treatment for Alzheimer’s disease
not been shown to reduce healthcare costs/delay institutionalization
can be used with memantine in moderate to severe disease
Galantamine
indirect acting reversible muscarinic agonist
first line treatment for alzheimer’s disease
has not been shown to reduce healthcare costs/ delay institutionalization
can be used with memantine
What do antimuscarinic agents do?
blocks the muscarinic receptor and inhibits muscarinic function
What do ganglionic blockers do?
blocks the entire output of ANS at the nicotinic receptor
What do neuromuscular blockers do?
block cholinergic transmission between motor nerve endings and the nicotinic receptors on the skeletal muscles
Ipatropium
muscarinic antagonist
derivatives of atropine, bronchodilator
used to treat COPD
Tropicamide
muscarinic blocker
duration of action is shorter than atropine
in ophthalmology used to produce mydriasis and cycloplegia prior to refraction
Cyclopentolate
muscarinic blocker
duration of action is shorter than atropine
in ophthalmology used to produce mydriasis and cycloplegia prior to refraction
Benztropine
muscarinic blocker
adjuncts with other antiparkinsonian agents
used to treat Parkinson’s disease
Trihexyphenidyl
muscarinic blocker
adjuncts with other antiparkinsonian agents
used to treat Parkinson’s disease
Darifenacin
muscarinic blocker
synthetic atropine-like drug
used to treat overactive urinary bladder
Fesoterodine
muscarinic blocker
synthetic atropine-like drug
used to treat overactive urinary bladder
Solifenacin
muscarinic blocker
synthetic atropine-like drug
used to treat overactive urinary bladder
Tolterodine
muscarinic blocker
synthetic atropine-like drug
used to treat overactive urinary bladder
Trospium Chloride
muscarinic blocker
synthetic atropine-like drug
used to treat overactive urinary bladder
Adverse effects of muscarinic antagonists
blurred vision
confusion
mydriasis
constipation
urinary retention
Dopamine
ganglionic blocker
pleasure
appetite suppression
catecholamine
alpha 1 and beta 1 receptors
treats shock and congestive heart failure
raises blood pressure
increased cardiac output, increased blood flow
Norepinephrine
ganglionic blocker
arousal
appetite suppression
Glutamate
ganglionic blockers
learning + memory enhancement
NMDA receptors- calcium and sodium channels
in the brian
neuronal excitation
synaptic plasticity
excitotoxicity
Serotonin
ganglionic blocker
mood modulation
appetite suppression
5HT3 receptor
excitatory; gates sodium, potassium, and calcium ions
in the CNS and PNS
nauesea and vomiting, anxiety, seizure propensity, pro-nociception
Beta Endorphin
ganglionic blocker
anxiety and tension reduction
GABA
ganglionic blocker
anxiety and tension reduction
receptor is inhibitory and gates Cl^-
major inhibitory transmitter in the CNS
hyperpolarizes cell membranes
decreases neuronal fibrin rate
in the CNS
anxiolytic, anticonvulsant, amnesic, sedative, hypnotic, muscle relaxant
Blocking sympathetic ganglion means
reduction in norepinephrine release
reduction in heart rate and blood pressure
Blocking parasympathetic ganglion means
reduction in ACh release
increase in heart rate
Nondepolarizing competitive neuromuscular blocking drugs
pancuronium, vecuronium, cistracurium, rocuronium
highly polar compounds that are poorly absorbed from the GI tract; preferred parenteral admin
low doses competitively block ACh at the nicotinic receptors
high doses block the ion channels of the motor endplate, leads to weakening of neuromuscular transmission, resulting in decrease of the ability of AChE inhibitors to reverse nondepolarizing blocker’s action
used for muscle relaxation during general anesthesia and in the lethal injection cocktail
safe with minimal side effects
Depolarizing neuromuscular blocking agents
succinylcholine
binds to the nAChR and acts like ACh to depolarize the junction
rapid onset
used for rapid endotracheal intubation during the induction of anesthesia, electronvulsive shock treatment
adverse effects: hyperthermia, apnea, hyperkalemia
Adrenergic drugs affect receptors stimulated by
norepinephrine and epinephrine
Sympathomimetics
adrenergic drugs activating adrenergic receptors
Sympathy lyrics
drugs blocking the activation of adrenergic receptors
What does DOPA stand for?
dihydroxyphenyalanine
prodrug
What does COMT stand for?
catechol-O-methyltransferase
What does MOA stand for?
monoamine oxidase
What does SNRI stand for?
serotonin-norepinephrine reuptake inhibitor
Steps for the release of norepinephrine from the adrenergic neuron
- hydroxylation of tyrosine makes dopamine
- uptake into storage vesicles and converted to norepinephrine
- Norepinephrine is released into the synaptic cleft
- Norepinephrine binds to receptors
- norepinephrine is taken back up into the neuron
- norepinephrine is methylated by COMT and. oxidized by MAO
alpha1 adrenoreceptors
on postsynaptic membrane of the effector organs
leads to constriction of smooth muscle
GPCR- generates IP3 and DAG which turns on cytosolic proteins and releases calcium ions
alpha 2 adrenoreceptors
on presynaptic nerve endings
decreases NE release and inhibits cAMP production
inhibits release of ACh
What are the effects of alpha1 receptors?
vasoconstriction
increased peripheral resistance
increased blood pressure
mydriasis
increased closure of internal sphincter of the bladder
What are the effects of alpha2 receptors?
inhibition of norepinephrine release
inhibition of ACh release
inhibition of insulin release
What are the effects of beta1 receptors?
tachycardia
increased myocardial contractility
increased release of renin
What are the effects of beta 2 receptors?
vasodilation
decreased peripheral resistance
bronchodilation
increased muscle and liver glycogenolysis
increased release of glucagon
relaxed uterine smooth muscle
increase plasma glucose concentration
What are the effects of beta 3 receptors?
increased lipolysis
relaxation of detrusor muscles
Catecholamines
compounds containing a 3,4-dihydroxybenzene group
high potency to activate receptors
rapid inactivation due to metabolism by COMT and MOA
polar -> poor penetration into the CNS
brief duration of action
not admin orally
epinephrine
norepinephrine
isoproterenol
dopamine
Noncatecholamines
compounds w/o catechol hydroxyl groups
longer half lives since they are not inactivated by COMT
poorly metabolized by MOA
increased lipid solubility -> greater access to CNS
phenylephirine
ephedrine
amphetamine
Epinephrine
alpha 1 and alpha 2, beta 1 and beta 2 receptors
catecholamine
treats acute asthma and anaphylactic shock
used to treat cardiac arrest, bronchodilation, bronchospasm
used in local anesthetics to increase duration of action
increases heart rate and blood pressure
Norepinephrine
catecholamine
alpha 1, alpha 2, and beta 1 receptors
used in the treatment of shock
increases heart rate, blood pressure, and vascular resistance
Isoproterenol
catecholamine
beta 1 and beta 2 receptors
cardiac stimulant
increase cardiac output
peripheral vasodilation, bronchodilation
Dobutamine
catecholamine
beta 1 receptor
treats acute heart failure
Oxymetazoline
Noncatecholamine
alpha 1 receptor
nasal decongestant
Phenylephrine
noncatecholamine
alpha 1 receptor
nasal decongestant
raise blood pressure
treats paroxysmal suprventricular tachycardia
Clonidine
noncatecholamine
alpha 2 receptor
treatment of hypertension
Albuterol
noncatecholamine
beta 2 receptor
treatment of short acting bronchospasm
Terbutaline
noncatecholamine
beta 2 receptor
treatment of short acting bronchospasms
Salmeterol
noncatecholamines
beta 2 receptor
treatment of long acting bronchospasms
Formoterol
noncatecholamine
beta 2 receptor
treatment of long acting of bronchospasm
Amphetamine
noncatecholamines
alpha and beta receptors, CNS
treats kids with ADD and narcolepsy
helps with appetite control
Ephedrine
Noncatecholamine
alpha and beta receptors, CNS
nasal decongestant
raises blood pressure
Pseudoephedrine
Noncatecholamine
alpha and beta receptors, CNS
nasal decongestant
raises blood pressure
Adverse effects of adrenergic agonists
arrhythmias
headache
hyperactivity
insomnia
nausea
tremors
Adrenergic antagonists
adrenergic blockers
sympatholytics
reversible/irreversibly bind to adrenergic receptor
prevent receptor activation by endogenous catecholamines
primarily used to relieve complications of cardiovascular disease
Alpha adrenergic antagonists
blockade of alpha adrenergic receptors
inhibit vasoconstriction of blood vessels
decrease peripheral vascular resistance
decrease blood pressure
Phenoxybenzamine
nonselective alpha adrenergic agonist
non competitive
Phentolamine
nonselective alpha adrenergic antagonist
competitive
Adverse effects of alpha adrenergic antagonists
provoke reflex tachycardia
syncope
orthostatic hypotension
tachycardia
dizziness and headache
sexual dysfunction
Prazosin
alpha adrenergic antagonist
selective alpha 1 blocker
competitive
treats hypertension
adverse reactions: tachycardia, dizziness, headache, sexual dysfunction
Terazosin
alpha adrenergic antagonist
selective alpha 1 blocker
competitive
treats hypertension
adverse reactions: tachycardia, dizziness, headache, sexual dysfunction
Doxazosin
alpha adrenergic antagonist
selective alpha 1 blocker
competitive
treats hypertension
adverse reactions: tachycardia, dizziness, headache, sexual dysfunction
Alfuzosin
alpha adrenergic antagonist
selective alpha 1 blocker
competitive
treats hypertension
adverse reactions: tachycardia, dizziness, headache, sexual dysfunction
Tamsulosin
alpha adrenergic antagonist
selective alpha 1 blocker
competitive
treats hypertension
adverse reactions: tachycardia, dizziness, headache, sexual dysfunction
Yohimbe
alpha adrenergic antagonist
selective alpha 2 blocker, competitive
treats erectile dysfunction
increases sympathetic outflow from the CNS to the periphery
Blockade of beta adrenergic receptors
inhibit NE release
decreased heart rate, heart contractility, cardiac output, renin activity
Which receptors do nonselective Beta adrenergic antagonists act on?
both beta 1 and beta 2
Propranolol
adrenergic antagonists
Beta 1 and Beta 2 receptor
used to treat hypertension, migraine, hyperthyroidism, angina pectoris, myocardial infarction
Nadolol
adrenergic antagonist
Beta 1 and beta 2 receptors
treats hypertension
Pindolol
adrenergic antagonist
Beta 1 and beta 2 receptors
treats hypertension
Timolol
beta adrenergic antagonists
beta 1 and beta 2 receptors
used to treat hypertension and glaucoma
Atenolol
beta adrenergic antagonists
beta 1 receptor
used to treat hypertension, angina, myocardial infarction
Bisoprolol
beta adrenergic antagonists
beta 1 receptor
used to treat hypertension, angina, myocardial infarction
Esmolol
beta adrenergic antagonists
beta 1 receptor
used to treat hypertension, angina, myocardial infarction
Metoprolol
beta adrenergic antagonists
beta 1 receptor
used to treat hypertension, angina, myocardial infarction
Acebutolol
beta adrenergic antagonists
beta 1 receptor
used to treat hypertension
Nebivolol
beta adrenergic antagonist
beta 1 receptor, increased nitric oxide
treats hypertension
Carvedilol
beta adrenergic antagonist
alpha 1, beta 1, and beta 2 receptors
treats hypertension
Labetalol
beta adrenergic antagonist
alpha 1, beta 1, and beta 2 receptors
treats hypertension
Adverse effects of Beta adrenergic antagonists
fatigue
bronchoconstriction
sexual dysfunction
arrhythmias
How many distinct ion channels do humans express?
200
Ion channels regulate the passive diffusion of these through cell membranes:
sodium, potassium, calcium, and chloride
What are the types of ion channels?
voltage activated
ligand activated
store activated
stretch activated
temperature activated
Where are ion channels that generate action potential?
excitable tissues
Where are ion channels that trigger cellular biochemical and secretory events?
non-excitable tissues
Sodium
binds to voltage gated ion channels
inhibits peripheral neurotransmission- local anesthetics
involved in transmission of myocardial action potential- class 1 antiarrhythmic drugs
Potassium
expressed in nerve, cardiac and smooth muscle tissues
regulates resting membrane potential
class 3 antiarrhythmic drugs prolong repolarization of cardiac action potentials
Where is calcium widely distributed in?
nerves- stimulates release of neurotransmitters
myocardium- class 4 antiarrhythmic drugs, depolarization of pacemaker, modification of shape and duration of myocardial action potential
smooth muscle- calcium channels regulate vascular tone, calcium channel blockers dilate blood vessels
Acetylcholine ligand-gated ion channels: somatic neuromuscular transmission
agonist- carbachol
antagonist- pancuronium, alpha bungarotoxin
Acetylcholine ligand-gated ion channels: sympathetic and parasympathetic autonomic ganglia
agonist- nicotine
antagonist- trimetaphan
Acetylcholine ligand-gated ion channels: CNS
3 subtypes involved in attention, addiction, and cognition
agonist- nicotine
antagonist- bupropion
Bicuculline
antagonist at GABA binding sites
Allosteric agonist modulators of GABA
barbiturates
ethanol
benzodiazepines
propofol
What are the agonists of glutamate?
glutamic acid and glycine
What are the antagonists of glutamate?
ketamine, Mg^2+, memantine
What are the agonists of serotonin ?
ethanol
ibogaine
What are the antagonists of serotonin?
ondansetron, clozapine
Glycine receptor
involved in sensory and motor function
binds the inhibitory neutrotransmitter glycine; gates chloride channels
in the CNS
What are the glycine receptor agonists?
glycine and taurine
What are the glycine receptor antagonists?
picrotoxin
strychnine
If the G protein heterotrimer forms a complex with GDP there is no?
ligand present
What binds to and regulates effectors?
GTP bound G alpha subunit and beta gamma dimer
GTP is inactivated by
hydrolysis
Prolonged stimulation of GPCR can lead to
downregulation of the receptor
G protein receptor kinases
phosphorylate the C terminal tail on the receptor and recruit proteins known as arrestins
Arrestins
binds to the receptor on the internal surface, displace g proteins and inhibit signaling
GPCR Gi
inhibition of adenyly cyclase and decrease in cAMP
Adenosine, melatonin, opioids, and acetylcholine all bind to which type of GPCR receptor?
Gi
GPCR Gq
second messengers
IP3- binds to and releases Calcium ions from the endoplasmic/ sarcoplasmic reticulum
DAG- activates kinase PKC
Ca^2+ -binds to and activates intracellular proteins and enzymes
PKC- phosphorylates and activates/deactivates intracellular enzymes
pharmacological response to receptor activation by the agonist
Agonists that activate Gq GPCRs
NE- alpha 1- vascular smooth muscle contraction
Thromboxane A2 - platelet aggregation
ACh- M3- smooth muscle contraction and glandular secretion
