Exam 3 Flashcards
Effects of Ach on CNS & PNS.
CNS: arousal, reward, and attention
PNS: skeletal muscle contraction, cardiac muscle relaxation, SLUDGE
Effects of DA on CNS and PNS.
CNS: motor control, cognition, reward, sexual arousal, motivation, and mood.
PNS: increased renal clearance and decreased gut motility.
Effects of glutamate.
most common excitatory NT which functions in learning/memory and cell death/ischemia.
Effects of NE on CNS & PNS.
CNS: attention, alertness, energy, reward, cognition
PNS: sympathetic activation
Effects of 5-HT on CNS & PNS.
CNS: relaxation, pleasure, obsession, and compulsion
PNS: blood clotting and increased GI motility
What does VNT stand for? How does it work?
vesicular neurotransmitter transport - push NTs against their concentration gradient into acidified lipid vesicles via proton anti-porters
Explain NT release.
Action potential –> Ca2+ opens –> binding activates SNARE complex which docks vesicles –> NTs squeezed out into synaptic cleft.
Botulinum toxin effect.
blocks the SNARE complex & release of excitatory NTs, causing paralysis and sometimes respiratory failure.
Tetanus toxin effect.
blocks the SNARE complex and release of inhibitory NTs, causing muscle spasms and lock jaw.
What are the two classes of NT receptors?
- Ionotropic: ligand gated ion channels.
2. Metabotropic: g-protein coupled receptors.
AcH receptors.
- Nicotinic: Na+ channels.
2. Muscarinic: M1/3/5 Gq coupled, M2/4 Gi coupled.
DA receptors.
- D1/5 Gs coupled, D2/3/4 Gi coupled.
GABA receptors.
- GABAa: Cl- channels.
2. GABAb: Gi coupled.
Glutamate receptors.
- Na+/Ca2+ channels.
2. R1/5 Gs coupled, R2/3/4 Gi coupled.
NE receptors.
- Beta: Gs coupled.
- Alpha-1: Gq coupled.
- Alpha-2: Gi coupled.
5-HT receptors.
- 5-HT3: Na+ channels.
- 5-HT1/5: Gs coupled
- 5-HT2: Gq coupled.
- 5-HT4/6/7: Gi coupled.
MAO function.
enzyme which metabolizes 5-HT, DA, and NE (1st step).
COMT function.
Breaks down DA and NE (2nd step).
Mechanism of Cocaine.
Competitive inhibition of DA reuptake transporters which enhances the synaptic duration of dopamine.
Effects of cocaine.
- Mesocortical: stimulant effects.
2. Mesolimbic: changes within nucleus accumbens (reward center - addicting effect)
Side effects of cocaine.
Stroke, heart attack, hyperthermia, arrhythmias, and death.
Meth structure.
Phenethylamine
Meth mechanism.
Acts as a substrate for monoamine transporters which results in reversal of the transporter & forced release of the NT (meth = dopamine, MDMA = serotonin).
Meth effects.
- psycho-stimulant which enhances alertness and arousal.
2. MDMA has addition euphoric and empathogenic effects because it is mediated through serotonin.
Overall, what’s the most important receptor targeted by psychedelics? What are the three classes of psychedelics?
5-HT. (specifically, 5-HT2a/c)
- Phenethylamines.
- Tryptamines.
- Lysergamides.
What is the difference between phenethylamines and tryptamines from lysergamides regarding receptor activity?
What was 2,5 methoxy modeled after? What does lacking the 2 methoxy groups yield?
Lysergamides activates dopamine and alpha-2 receptors on top of 5-HT receptors.
2,5-methoxy was modeled after mescaline and produces hallucinogenic and psychedelic effects.
Lacking the 2 methoxy groups yields psycho-stimulant and/or empathetic effects.
What are the classes of cholinergic agents and what do they do?
- Neuromuscular Blocking Agents: block activity of Ach receptors in the somatic system.
- AchE Inhibitors: block Ach esterase.
- Antimuscarinics: block muscarinic receptors.
What is curare and what is its function?
Alkaloid molecule originally used for hunting that acts as a reversible, competitive antagonist for nicotinic-Ach receptors at the NMJ.
Causes paralysis and asphyxiation.
Structure and action of depolarizing NMJ blockers.
- Flexible, linear structures (close analogs to ach)
- Initially activate (depolarize) the receptor. Persistent activation causes receptor desensitization and inactivation. Basically, Ca2+ gets sequestered and causes the muscle to relax.
What class is succinylcholine in? How does it work.
NMJ blocker.
NOT a substrate for Ach esterase and is instead metabolized by plasma cholinesterase. In order for it to be broken down, sux must diffuse out of the NMJ. This allows for longer duration activity at the NMJ necessary for receptor desensitization.
Structure and actions of non-depolarizing NMJ blockers.
- Large, bulky, and/or rigid structures with hydrophobic surfaces. Common structure is two positively charged nitrogen atoms spaced apart.
- Function as competitive inhibitors, similar to curare.
Name the 3 SAR modifications for NMJ blockers and what they cause.
- Rigidity (non-depolarizing) increases potency.
- Optimum distance from N+ to N+ is 2.1 nm. Larger molecules tend to be non-depolarizing.
- Lipophilicity increases non-depolarizing likelihood.
Name the uses of NMJ blockers.
- Paralytic agent during anesthesia.
2. Aids in intubation process.
Side effects of depolarizing NMJ blockers.
- Hyperkalimia.
- Pain from fasciculations.
- cardiovascular effects (arrhythmias)
Side effects of non-depolarizing NMJ blockers.
- can induce histamine.
2. tachycardia.
Acetylcholinesterase structure and function.
Contains anionic (binds to acetylcholine’s N+ group) and esteric/catalytic (catalytic triad composed of 3 amino acid residues glutamate, histidine, and serine which undergo the mechanism).
cleaves acetylcholine into acetate and choline.
Explain the mechanism of acetylcholinesterase.
- Histidine activates the nucleophilic serine residue.
- Serine binds to the Ach via nucleophilic attack, forming an acetylated intermediate.
- Hydrolysis via H2O molecules releases acetate from the serine active site which completes the cycle.
- Acetate and choline diffuse away from the enzyme which returns AchE to its active state.
Explain how AchE inhibitors.
Increases ach so that it can outcompete non-depolarizing NMJ blockers. (reverses their effects).
What are AchE inhibitors commonly given with? Why?
Atropine (non-selective antagonist of muscarinic receptors) to prevent bronchoconstriction caused from increased Ach.