Midterm 1

Question 0

Carbamylcholine

Answer 0

Classic nAChR agonist, often used in replacement of ACh in the lab.

Question 1

Varenicline (Chantix)

Answer 1

Partial agonist at alpha 4 beta 2 subtype, non-nicotine aid to smoking cessation.

Question 2

Succinylcholine (suxamethonium)

Answer 2

Depolarizing muscle relaxant. Causes excitation, but instead of causing muscle contraction it causes muscle relaxation. Not well metabolized by AChE, which means that the response is not able to be terminated resulting in prolonged depolarization. When the membrane is depolarizer for a long time, it stops firing action potentials because the sodium channels become deavtivated in response to prolonged depolarization.

Question 3

Tubocurarine

Answer 3

Component of curare found in plants. Used as arrow poisons. Competitive nAChR antagonist.

Question 4

Pancuronium

Answer 4

A reversible nAChR competitive antagonist that is used as a muscle blocker together with anesthetic during some surgery.

Question 5

Alpha-Bungarotoxin

Answer 5

Cobra and krait toxin. An irreversible nAChR antagonist.

Question 6

Bupropion

Answer 6

Smoking cessation therapeutic. Inhibits neuronal reuptake of dopamine and is a weak alpha 4 beta 2 nAChR antagonist.

Question 7

Hemicholinium

Answer 7

Inhibitor of Na+/Choline cotransporter. Blocks reuptake of choline into nerve terminal, thereby blocking the synthesis of ACh. Not pharmacologically useful but can be used in the lab if one wants to study the synthetic pathway of ACh.

Question 8

Vesamicol

Answer 8

Inhibitor of vesicular ACh transporter. ACh transporter exchanges ACh for protons to load the vesicles. Vesamicol has potential in mapping of cholinergic innervations in brain in vivo.

Question 9

Botulinum toxin

Answer 9

Blocks the release of ACh from presynaptic nerve terminals on skeletal muscle, paralyzes muscle. Made by an anaerobic bacteria that tends to grow in canned foods. Works by cleaving SNARE proteins that normally act in a calcium dependent manner to create a SNARE fusion complex between the SNAREs in the vesicles and plasma membrane. Used to treat muscle spasm, chronic migraine, sweating, and wrinkles. Preferentially cleaves SNARES in the periphery. Lifetime of about 3-4 months after being injected.

Question 10

Alpha-Latrotoxin

Answer 10

Black widow spider venom that promotes massive ACh release at neuromuscular junction by binding to presynaptic proteins, causing presynaptic calcium increases that trigger neurotransmitter release. Calcium activates the SNARE binding that allows for vesicles fusion to the membrane.

Question 11

Physostigmine, Neostigmine

Answer 11

Reversibly inactivate AChE. Used in the treatment of myasthenia gravis, which involves muscle weakness due to destruction of nicotinic receptors because the individual generates antibodies for their own receptors.

Question 12

Donepezil (Aricept)

Answer 12

AChE inhibitor that’s used in the treatment of Alzheimer’s Disease. One effect of Alzheimer’s is a decrease in cholinergic transmission in the brain. This treatment only had a moderate effect though, and it fails to treat the condition. Only makes use of the available receptors.

Question 13

Organophosphates (Insecticides and Nerve Gasses)

Answer 13

Covalently and irreversible inactivate AChE.

Question 14

GABA

Answer 14

Endogenous agonist of GABA A receptors. Requires Glutamic Acid Decarboxylase and pyridoxal phosphate to be synthesized

Question 15

Muscimol

Answer 15

Derived from hallucinogenic mushroom, resembles GABA chemically, powerful GABA A receptor agonist.

Question 16

Gaboxadol

Answer 16

Synthetic analogue, partial agonist.

Question 17

Bicuculline

Answer 17

Naturally occurring convulsant compound, is a specific competitive antagonist that blocks fast inhibitory synaptic potential in most CNS synapses. Useful in lab.

Question 18

Gabazine

Answer 18

Synthetic GABA analogue. Antagonist.

Question 19

Picrotoxin

Answer 19

Channel blocker. Convulsant that acts by blocking chloride channel pore of GABA A receptor, thus blocking the postsynaptic inhibitory effect of GABA. Noncompetitive antagonist

Question 20

Benzodiazepines

Answer 20

Bind with high affinity to a separate site on GABA A receptors that is different from the agonist binding site for GABA. Alprazolam (Xanax), Clonazepam (Klonopin), Diazepam (Valium), Lorazepam (Ativan).

Question 21

Convulsant analogues

Answer 21

Flumazenil is a benzodiazepine antagonist; Beta-Carbolines are benzodiazepine inverse agonists.

Question 22

Barbiturates

Answer 22

CNS depressant.

Question 23

Anesthetic agents

Answer 23

IV anesthetic for fast-acting induction of anesthesia-propofol, etomidate, potentiate the effect of GANA.

Question 24

Neurosteroids

Answer 24

Allosterically enhance activation of GABA A receptors, as well as activating conventional intracellular steroid receptors.

Question 25

Name 3 allosteric modulators if GABA A receptors

Answer 25

Benzodiazepines, Barbiturates, Anesthetics and Neurosteroids.

Question 26

Anxiolytics

Answer 26

Benzodiazepines, barbiturates, 5-HT1A agonists, beta adrenergic receptor antagonists.

Question 27

Taurine

Answer 27

Partial agonist to glycine receptor.

Question 28

GABA A alpha 1 subunit

Answer 28

Sedation, anticonvulsant action, anterograde amnesia, addiction.

Question 29

GABA A alpha 2 subunit

Answer 29

Anxiolysis, antidepression, myorelaxation.

Question 30

GABA A alpha 3 subunit

Answer 30

Myorelaxation

Question 31

GABA A alpha 5 subunit

Answer 31

Affects spatial memory, cognitive impairment, myorelaxation.

Question 32

Strychnine

Answer 32

Competitive antagonist of Glycine receptor that causes spinal convulsions.

Question 33

Tetanus toxin

Answer 33

Inhibits glycine release in spinal cord, causing muscle rigidity. Tetanus is taken up by inhibitory interneurons in the spinal cord. Cleaves vesicle SNARE synaptobrevin.

Question 34

Botulinum Toxin

Answer 34

Taken up by excitatory motor neurons in spinal cord. Types B,D, F, and G cleave vesicle SNARE synaptobrevin. Type C cleaves plasma membrane SNARE syntaxin. Types A and E cleave plasma membrane SNARE SNAP-25.

Question 35

Ivermectin

Answer 35

Glutamate-Cl receptor allosteric agonist used to kill microfilariae that cause river blindness, and to a lesser extent to treat elephantitis.

Question 36

Piperazine

Answer 36

GABA agonist at invertebrate NMJ, effective at killing microfilariae that cause river blindness.

Question 37

Give 4 pharmacological methods of killing microfilariae that cause river blindness:

Answer 37

Ivermectin, piperazine, inhibitors of microtubule function, inhibitors of arachidonic acid metabolism.

Question 38

Nicotine

Answer 38

In CNS causes neural excitation, increased heart rate, increased blood pressure, highly addictive, causes cardiovascular problems.

Question 39

Acetylcholine

Answer 39

Made from acetylcoenzyme A and choline by choline acetyltransferase. Stimulates neuromuscular junction and postganglionic autonomic neurons.

Question 40

AMPA Receptors

Answer 40

Agonists: Glutamate, AMPA, Quisqualate.
Antagonists: NBQX, CNQX.

NA/K permeable, low Ca permeability, not blocked by Mg.

Can be activated at all membrane potentials; fast EPSP.

Question 41

NMDA Receptors

Answer 41

Agonists: Glutamate, NMDA, aspartate.
Co-Agonist: Glycine.
Antagonist: APV/AP5.
Channel blocker (noncomp antagonist): PCP, ketamine, MK801.

NA/K and Ca permeable, blocked by Mg.

Can only be activated at depolarized potentials; slow EPSP.

Question 42

GABA B Receptor

Answer 42

Located pre and postsynaptically. GPCR; functional receptor is a dimer. Inhibitory action by stimulating the opening of potassium channels and inhibiting voltage gated calcium channels.