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M1 Drugs

Match drugs and receptor types to function

What are the 3 main types of classical ntm? Monoamines (catecholamines, 5HT), Acetylcholine, Amino acids (GABA, glutamate)
What are the 5 types of non-classical ntm? Neuropeptides, lipids, gases, D-amino acids, purines
What are the 4 characteristics of classical neuromodulatory systems? subcortical, long projections to cortex, excitatory or inhibitory, for arousal/attention/motivation
What are the 2 metabolites of NE when broken down? For DA? MHPG, VMA for NE; HVA for DA
Dopa --> Dopamine needs which enzyme? AADC
Dopamine --> NE needs which enz? DBH (marker of NE cells)
NE --> EPIN needs which enz? phenylethanolamine-N-methyltransferase
The substantia nigra is a region in which ntm system and what does it control? DA. movement
The ventral tegmental area (VTA) is a region in which ntm system and what does it control? DA. reward/reinforcement, mood, concentration
What is the region of the DA system that controls olfaction? periglomerular cells
The tuberophypophysialincertohypothalamic is a region in which ntm system and what does it control? DA. hormones
In the DA system, how does D1-like receptors act? Which 2 receptors are they? Where are they? increase cAMP. D1, D5. Caudate-putamen, nucleus accumbens, olf, hippocampus, hypothalamus
In the DA system, how does D2-like receptors act? Which 3 receptors are they? decrease cAMP, open K+ channels, increase AA, decrease Ca++. D2, D3, D4
SKF38393. ntm system? receptor? fxn? DA. D1. agonist
fenoldopam. what else is it called? ntm system? receptor? fxn? SKF 82526. DA. D1. agonist
clozapine. ntm system? receptor? fxn? DA. D4. agonist... inhibitory since reduce cAMP
quinpirole. ntm system? receptor? fxn? DA. D2, D3. agonist.
pergolide. ntm system? receptor? fxn? DA. D2, D3. agonist.
apomorphine. ntm system? receptor? fxn? DA. D1, D2. agonist.
bromocriptine. ntm system? receptor? fxn? DA. D2. agonist
dihydrexidine. ntm system? receptor? fxn? DA. D1. agonist.
haloperidol. ntm system? receptor? fxn? DA, D2, antagonist
sulpiride. ntm system? receptor? fxn? DA, D2, antagonist
spiperone. ntm system? receptor? fxn? DA, D2, antagonist
YM-09151-2. ntm system? receptor? fxn? DA, D2. antagonist
S 14297. ntm system? receptor? fxn? DA, D3, antagonist
NNC-112. ntm system? receptor? fxn? DA, D1. antagonist
SCH 23390, SCH 39166. ntm system? receptor? fxn? DA, D1, antagonist
Describe the pathway after D1 and D2 receptors are bound by dopamine or a drug. receptor-->G protein-->AC-->cAMP-->PKC-->open Na+ ch. note: in D2-receptors less cAMP results in more open K+ channels
How many DA receptors are metabotropic? 5 (all)
What are the 3 pathways for DA? Which one is for reward? mesolimbic (reward), mesocortical, nigrostriatal
Where does VTA project to in the mesolimbic pathway for DA? nucleus accumbens, amygdala, lateral septum, olfactory tubercule
Where does VTA project to in the mesocortical pathway that the mesolimbic pathway doesn't for DA? prefrontal cortex, hippocampus
What 3 areas are involved in the reward pathway? VTA --> nucleus accumbens --> prefrontal cortex
Parkinson's is due to the death of what area of which neurons? substantia nigra, DA
What is the precursor for catecholamines? For 5HT? For glutamate? For GABA? For ACh? tyrosine. tryptophan. glutamine. glutamate. acetyl coa and choline.
increase catecholamine levels in brain by inhibiting MAO (MAOI) phenelzine
inhibits tyrosine hydroxylase. what ntm system? AMPT. DA
lowers catecholamine levels by inhibiting vMAT reserpine
6-OHDA. fxn? what system? lesions/kills catecholamine neurons (DA, NE)
what recreational drug causes more release of catecholamines? amphetamine
what recreational drug inhibits reuptake of catecholamines? cocaine
methylphenidate. fxn? what ntm system? same as cocaine - stops reuptake of catecholamines
apomorphine DA agonist, mainly D2 (DA)
agonists for D1 receptors (DA) SKF 38393, fenoldam
SCH 23390, NCC-112 antagonist for D1 receptor (DA)
quinpirole agonist for D2, D3 receptors (DA)
haloperidol antagonist for D2 (DA)
Locus Coeruleus (A6): where is it (approx)? where does it project to? what ntm system? fxn? pons. all of forebrain. NE. arousal (sleep/wake)
Which activates the locus coeruleus to increase vigilance: internal cues (grooming, sleep) or external cues? external
Paraventricular neurons are in the hypothalamus and receives NE to trigger what type of behavior? eating
NE receptors are called what? Are they metabotropic or ionotropic? adrenoceptors. all metabotropic
NE alpha 1 receptors do what? excitatory: phosphoinositide 2nd messenger system to increase Ca++
Describe NE alpha 2 receptor fxns. autoreceptor and receptor. inhibitory: inhibit AC-->decrease cAMP; open K+ channels
Describe NE beta 1 and 2 receptors' fxn. excitatory: stimulate AC-->increase cAMP
what drug selectively inhibit NE uptake? Nisoxetine (not cocaine or methylphenidate since for all catecholamines)
phenylephrine NE alpha 1 agonist
prazosin NE alpha 1 antagonist
clonidine NE alpha 2 agonist
Yohimbine NE alpha 2 antagonist
albuterol NE beta agonist, mainly beta 2
propanolol NE beta antagonist
metoprolol NE beta 1 antagonist
The raphe nucleus is for which ntm system? What are the 2 main nuclei (b7, b8)? serotonin. b7 = dorsal RN, b8 = medial RN
5HT is inactivated by which enzyme? What is the metabolite? MAO. 5-HIAA
Which 5HT receptor subtypes are autoreceptors? 1B, 1D
What does 5HT 1A receptor do? Where are 1A receptors found mostly? inhibitory (opp from catecholamines where subtypes 1 are excitatory and 2 are inhibitory)! decrease cAMP, open K+ ch. Found in hippocampus, DORSAL raphe nucleus, amygdala, septal area.
What does 5HT 2A receptor do? Where are 2A receptors found mostly? Excitatory: 2A receptor-->G protein-->PKC, increase Ca++. Found in cortex
Which ntm system uses PPI 2nd messenger system? which receptor subtype? NE. alpha 1
para-chlorophenylalanine 5HT. (similar to AMPT in catecholamine) inhibits tryptophan hydroxylase.
What 2 drugs inhibit 5HT uptake? SSRIs: fluoxetine, paroxetine
Paroxetine SSRI (prevent 5HT reuptake). fluoxetine is also a SSRI.
para-chloroamphetamine. can it be dangerous? increase 5HT release. yes - can be neurotoxic just like MDMA
MDMA increase 5HT release. neurotoxic
What drug increases 5HT release at nerve terminals but is NOT neurotoxic? fenfluramine
5,7-dihydroxytryptamine 5HT neurotoxin for lesioning. (similar to 6-OHDA in catecholamine system)
buspirone (buspar) 5HT 1A agonist --> less 5HT released, inhibitory
ipsapirone 5HT 1A agonist
8-OH-DPAT 5HT 1A agonist
WAY 100635 5HT 1A antagonist
DOI 5HT 2A agonist
Ketanserin 5HT 2A antagonist
Ritanserin 5HT 2A antagonist
Sumatriptan 5HT 1B/1D (autoreceptors) agonist, increase negative feedback on 5HT release (inhibitory)
Zolmitriptan 5HT 1B/1D (autoreceptors) agonist, increase negative feedback on 5HT release (inhibitory)
Ondansetron 5HT 3 antagonist
Granisetron 5HT 3 antagonist
What is the only 5HT ionotropic receptor? 5HT 3
What 6 regions in the striatum of the brain can ACh neurons be found? laterodorsal nuclei, pedunculopontine tegmental nucleus; nucleus basalis, substantia innominata; medial septum, diagonal band nuclei; caudate-putamen, nucleus accumbens
How do mAChR work? Inhibitory: many different mechanisms ie. PPI 2nd messenger, decrease cAMP, open K+ channels
Vesamicol inhibit vesicular loading (inhibit vAChT)
black widow spider venom. what is a drug that has the opposite effect? more release of ACh. botox
HC-3 inhibit choline (ACh) reuptake
physostigmine, neostigmine, pyridostigmine inhibit AChE reversibly, increases ACh in cleft
What 2 nerve gases irreversibly inhibit AChE? sarin, soman
nicotine nAChR agonist (duh...)
What is the other nAChR agonist besides nicotine? which is the stronger drug? succinylcholine is stronger since it can cause depolarization block
mecamylamine nAChR antagonist. same as D-tubocurarine
D-tubocurarine nAChR antagonist. same as mecamylamine and curare
muscarine mAChR agonist (duh...)
arecoline mAChR agonist. same as pilocarpine
pilocarpine mAChR agonist
Atropine mAChR antagonist. same as scopolamine (can treat motion sickness)
Scopolamine mAChR antagonist.
Where can glutamatergic neurons be found? Where do they project? Is it excit or inhib? pyramidal neurons (hippocampus), parallel fibers of cerebellum. project to striatum, brainstem, limbic system, thalamus. Excitatory
Glutamine-->glutamate needs what enzyme and reagents? glutaminase. water, ATP (the only ntm synthesis that needs energy so far!)
What are good markers for glutamate neurons? VGLUT1,2,3
How is glutamate inactivated? By reuptake via EAAT1,2,3 into neurons (3) or astrocytes (1,2)
Glutamine synthetase in astrocytes. glutmate-->glutamine
Do metabotropic glutamate receptors exist? If so, what mechanism(s) do they use? Yes, mGluR1-8. PPI 2nd messenger; inhibit cAMP; autoreceptors; but note - no mention of opening K+ channels
What enzyme converts glutamate to GABA? What is lost (fxnal group)? glutamic acid decarboxylase (GAD). CO2 is lost from backbone end.
What are GABA transporters called? What do they do? Are they also on glia? GAT1,2,3. Reuptake GABA from cleft. Yes they are on glia and on neurons.
What enzyme inactivates/break down GABA? What are the final breakdown pdts? Where can this enzyme be found? GABA-T = GABA aminotransferase. succinate, glutamate. Found in neurons and glia.
Glutamate and ____ neurons can be found in cerebellar cortex Gaba
Where do GABA neurons in the striatum project to? substantia nigra and globus pallidus
Where can GABA interneurons be found? cortex, hippocampus
What are the 2 types of GABA receptors? Which one is inhibitory? GABA a, GABA b. Both are inhibitory! B by inhibiting cAMP and opening K+ channels. A by letting in Cl- ions
Phenylcyclidine (PCP) NMDA (glutamate) noncompetitive antagonist. same as ketamine
What are 2 noncompetitive antagonists of NMDA (glutamate)? ketamine, pcp
How many subunits do GABA A receptors have? Where does BDZ bind? What about barbiturates? 5. on gamma or delta subunit. barbiturates on beta
What is the endogenous ligand for cannabinoid receptors? anandamide
What are the endogenous ligands for opiate receptors? endorphins, enkephalins
Created by: xiaohes