Patrick Tb Ch19

8/10/2019 Patrick Tb Ch19

1/41

Patrick: An Introduction to Medicinal Chemistry 3e

Chapter 19: Cholinergics, anticholingergics and anticholinesterases

Type: matching questionTitle:Chapter 19 - Question 0101) Consider the ollo!in" dia"ram#

$hat receptors are present to recei%e the neurotransmitter released at the synapses A-&'Feedback:(er%es inner%atin" skeletal muscle release acetylcholine as the neurotransmitter and !illinteract !ith choliner"ic receptors on skeletal muscle cells# here are t!o types o choliner"ic receptorand skeletal muscle contains nicotinic choliner"ic receptors rather than muscarinic receptors#*mooth muscle and cardiac muscle also ha%e choliner"ic receptors+ and these are muscarinic receptorsand not nicotinic receptors# (er%es o the parasympathetic ner%ous system release acetylcholine#,nlike skeletal muscle+ smooth muscle and cardiac muscle also ha%e adrener"ic receptors !hich areacti%ated y noradrenaline# (oradrenaline is released y ner%es o the sympathetic ner%ous system andacti%ation o adrener"ic receptors !ill ha%e the opposite eect on a tar"et cell rom the eect resultin"rom acti%ation o a choliner"ic receptor#he neurotransmitter released in the synapses et!een dierent ner%es or et!en a ner%e and the

adrenal medulla is acetylcholine and the receptor on the tar"et cell is a nicotinic receptor#Page reference:./0a# A (icotinic receptor 1)# 2 Adrener"ic receptorc# C Muscarinic receptord# (icotinic receptor 4)e# 5 (icotinic receptor 3)# & (icotinic receptor 6)

Type: matching questionTitle:Chapter 19 - Question 0404) Consider the ollo!in" dia"ram#

OXFORDH i g h e r E d u c a t i o n7 8ord ,ni%ersity Press+ 400/# All ri"hts reser%ed#


2/41


$hat are the names o the ner%ous systems indicated y and ;'Feedback:(er%es o the sympathetic ner%ous system synapse


3/41


$hat is the name o the chemical messen"er I) released y the adrenal medulla'Feedback:Adrenaline is released y the adrenal medulla and acts as a hormone# It tra%els round theody and acti%ates adrener"ic receptors# (oradrenaline+ acetylcholine and dopamine are allneurotransmitters released y speciic ner%es#

Page reference:./0a# (oradrenaline# Acetylcholine>c# Adrenalined# opamine

Type: matching questionTitle:Chapter 19 - Question 0606) Identiy the ollo!in" chemical messen"ers

Feedback:Acetylcholine and noradrenaline are neurotransmitters released y ner%es# Adrenaline is ahormone released y the adrenal medulla# Adrenaline and noradrenaline are %ery similar in structure andare classed as catecholamines# he term =nor= is oten used to indicate that the structure no lon"er has amethyl "roup on a nitro"en atom# hus noradrenaline has the same structure as adrenaline+ ut lacks the(-methyl "roup present on adrenaline#Page reference:./0a# A Acetylcholine# 2 (oradrenalinec# C Adrenaline



4/41


Type: multiple choice questionTitle:Chapter 19 Question 0.0.) $hat is the name o the en?yme responsile or the synthesis o acetylcholine'Feedback:Acetylcholinesterase catalyses the reakdo!n o acetylcholine# Choline acetyltranserasecatalyses its synthesis# he other t!o en?ymes do not eist#

Page reference:./4a# Acetylcholinesterase># Choline acetyltranserasec# Acetylcholine synthased# Acetylcholine li"ase

Type: matching questionTitle:Chapter 19 - Question 0/0/) he ollo!in" t!o compounds are natural products#

$hat are they called'Feedback:(icotine is present in toacco and contains a pyridine rin" linked toa pyrrolidine rin"#Muscarine is the acti%e principle o a poisonous mushroom and contains a tetrahydrouran rin"#Page reference:./6a# A (icotine# 2 Muscarine

Type: multiple choice question

Title:Chapter 19 Question 0@0@) he ollo!in" t!o compounds are natural products#

$hat eect do these structures ha%e on choliner"ic receptors'Feedback:2oth these a"ents act as a"onists at t!o dierent types o choliner"ic receptor# (icotine is ana"onist or nicotinic receptors# Muscarine is an a"onist or muscarinic receptors#

Page reference:./6-./.a# hey are suicide sustrates# hey are anta"onists>c# hey are a"onistsd# hey are allosteric modulators

Type: multiple choice questionTitle:Chapter 19 Question 00) $hich eature o acetylcholine interacts !ith the indin" site o choliner"ic receptors y ionic ondin"'



5/41


Feedback:he acyl methyl "roup its a hydrophoic pocket and interacts y %an der $aals interactions#he oy"en atoms o the ester ser%e as hydro"en ond acceptors to aspara"ine /1@ in the indin" site#he c# he


6/41


Page reference:.//a# *erine># Aspara"inec# lutamined# Cysteine

Type: multiple choice questionTitle:Chapter 19 Question 1414) ;o! many hydrophoic pockets in the choliner"ic indin" site are occupied y "roups present onacetylcholine'Feedback:here are three hydrophoic pockets# 8ne accepts the acyl methyl "roup# he remainin" t!oaccept t!o o the three N-methyl "roups#Page reference:.//a# 1# 4>c# 3d# 6


Title:Chapter 19 Question 1313) *e%eral aromatic amino acid residues present in the choliner"ic indin" site are thou"ht to interact!ith acetylcholine y means o an induced dipole-dipole interaction# $hich part o the acetylcholine isin%ol%ed'Feedback:he d# he


7/41


# It interacts !ith a hydrophoic pocket in the indin" site#>c# It acts as a steric shield to protect the ester "roup#d# It has an inducti%e eect on the nei"hourin" ester "roup#

Type: multiple choice questionTitle:Chapter 19 Question 1/

1/) he ollo!in" structure is a choliner"ic a"onist#

$hat is the structure called'Feedback:Compared to acetylcholine+ methacholine contains an etra methyl sustituent on the 4-Cchain linkin" the ester and d# 2ethanechol

Type: multiple choice questionTitle:Chapter 19 Question 1919) $hich o the ollo!in" structures !ould you epect to e a stale choliner"ic a"onist'



8/41


9/41


44) $hat are the products arisin" rom the hydrolysis o acetylcholine'Feedback:Page reference:./4a# 5thanoic acid and ethylamine# Methanoic acid and choline>c# 5thanoic acid and choline

d# 5thanoic acid+ ethanol and ammonia

Type: multiple choice questionTitle:Chapter 19 Question 4343) $hich o the ollo!in" is not an application or a muscarinic anta"onist'Feedback:*keletal muscle cells ha%e nicotinic receptors and so they are not aected y muscarinicanta"onists#Page reference:.@0-.@1a# 8phthalmic eaminations# *huttin" do!n the "astrointestinal and urinary tracts durin" sur"eryc# reatment o motion sickness>d# elaation o skeletal muscle

Type: multiple choice questionTitle:Chapter 19 Question 4646) $hich o the ollo!in" is not a "eneral characteristic o muscarinic anta"onists'Feedback:his is a re


10/41


$hat is the name o the structure'

Feedback:uocurarine is the acti%e principle o the natural etract curare# uocurarine !as the leadcompound leadin" to the synthetic a"ents suamethonium and pancuronium#Page reference:[email protected].@/>a# uocurarine# Curarec# *uamethoniumd# Pancuronium

Type: multiple choice questionTitle:Chapter 19 Question 4@4@) uocurarine is a lead compound or a class o medicinally useul compounds#

$hat !as the source o the structure'Feedback:Curare is the name o the plant etract rom !hich tuocurarine is isolated#Page reference:[email protected]# A marine coral# A poison toadstool>c# A plantd# *nake %enom

Type: multiple choice questionTitle:Chapter 19 Question 44) uocurarine is a lead compound or a class o medicinally useul compounds#



11/41


$hat sort o acti%ity does the ao%e structure ha%e'

Feedback:*keletal muscle cells ha%e nicotinic receptors# his a"ent acts as an anta"onist and not ana"onist#Page reference:[email protected]# Muscarinic a"onist# Muscarinic anta"onistc# (icotinic a"onist>d# (icotinic anta"onist

Type: multiple choice questionTitle:Chapter 19 Question 4949) Pancuronium is used as a neuromuscular locker#

$hat is the role o the steroid skeleton'Feedback:he crucial role o the steroid skeleton is to act as a spacer to ensure that the t!o c# It acts as a spacer to ensure that the


12/41


Type: multiple choice questionTitle:Chapter 19 Question 3030) Pancuronium is used as a neuromuscular locker#

$hat is the si"niicance o the lue re"ions o the molecule'

Feedback:he acetylcholine moieties !ere incorporated to increase the reco"nition o the dru" y thenicotinic receptor#Page reference:.@@>a# hey represent the skeleton o acetylcholine## hey are polar "roups !hich increase !ater soluility#c# hey introduce a dipole moment to the molecule allo!in" correct ali"nment o indin" "roups !hen themolecule inds to the indin" site#d# hey are prone to metaolism+ thus limitin" the lietime o the dru"#

Type: matching questionTitle:Chapter 19 - Question 3131) he ollo!in" structures !ere introduced as neuromuscular lockin" a"ents#

$hat are structures A) and 2) called'Feedback:ecamethonium and suamethonium are simple acyclic neuromuscular lockers# Decuroniumis a neuromuscular locker !hich contains a steroid skeleton as a spacer# Atracurium is a neuromuscularlocker !hose structure is related to elements o tuocurarine and suamethonium#Page reference:.@/-.@@a# A ecamethonium# 2 *uamethonium

Type: multiple choice questionTitle:Chapter 19 Question 3434) he ollo!in" structures !ere introduced as neuromuscular lockin" a"ents#

*tructure 2 is deri%ed rom structure A and has t!o ester "roups incorporated# $hat !as the main reason

or incorporatin" these "roups'



13/41


Feedback:*tructures A and 2 are decamethonium and suamethonium respecti%ely# Incorporation oester "roups !as desi"ned to reduce the lietime o the dru" since the esters are susceptile to en?ymatichydrolysis#Page reference:.@/-.@@a# o enhance hydro"en ondin" interactions !ith the indin" site## o increase the polarity o the dru"#

c# o alter the conormation o the molecule#>d# o reduce the lietime o the dru"#

Type: multiple choice questionTitle:Chapter 19 Question 3333) Atracurium is used intra%enously as a neuromuscular locker#

$hat t!o dru"s !ere used as the asis or the desi"n o this dru"'Feedback:he cyclic portions at either end are deri%ed rom tuocurarine !hile the chain containin" thet!o ester "roups is ased on suamethonium#Page reference:.@@-.@a# uocurarine and decamethonium# Decuronium and suamethonium

>c# uocurarine and suamethoniumd# Atracurium and mi%acurium

Type: multiple choice questionTitle:Chapter 19 Question 3636) Atracurium is used intra%enously as a neuromuscular locker#

$hich eature is chiely responsile or the dru"=s acti%ity and its rapid chemical de"radation'Feedback:he presence o t!o


14/41


Type: multiple choice questionTitle:Chapter 19 Question 3.3.) Acetylcholine is inacti%ated y the en?yme acetylcholinesterase#$hat is the reaction catalysed y this en?yme'Feedback:he en?yme catalyses the hydrolysis o acetylcholine to ethanoic acid and choline#Page reference:./4

>a# 5ster hydrolysis# eductionc# 8idationd# N-demethylation

Type: multiple choice questionTitle:Chapter 19 Question 3/3/) Acetylcholine is inacti%ated y the en?yme acetylcholinesterase#$hat amino acid in the acti%e site orms an interaction !ith the c# Aspartic acidd# ;istidine

Type: multiple choice questionTitle:Chapter 19 Question 3@3@) Acetylcholine is inacti%ated y the en?yme acetylcholinesterase#$hat amino acid in the acti%e site orms an interaction !ith the ester "roup o acetylcholine'Feedback:he phenolic "roup o tyrosine acts as a hydro"en ond donor to the ester "roup oacetylcholine#Page reference:.1-.4a# *erine># yrosine

c# Aspartic acidd# ;istidine

Type: multiple choice questionTitle:Chapter 19 Question 33) Acetylcholine is inacti%ated y the en?yme acetylcholinesterase#;o! many o the N-methyl "roups interact !ith hydrophoic pockets !ithin the acti%e site'Feedback:his is %ery similar to the indin" site o the choliner"ic receptor !hich has t!o hydrophoicpockets that can accomodate t!o o the three (-methyl "roups#Page reference:.1-.4a# 1># 4c# 3

d# 6

Type: multiple choice questionTitle:Chapter 19 Question 3939) Acetylcholine is inacti%ated y the en?yme acetylcholinesterase#$hich amino acid plays an important role as a nucleophile in the en?yme=s mechanism o action'Feedback:he hydroyl "roup o serine acts as a nucleophile in the en?yme=s mechanism o action#Page reference:.1-.4a# Bysine# ;istidine>c# *erined# hreonine

Type: multiple choice questionTitle:Chapter 19 Question 60



15/41


60) he ollo!in" compound is a natural product !hich inhiits the acetylcholinesterase en?yme#

$hat !as the natural source o this compound'Feedback:he calaar ean !as the natural source or physosti"mine# he coca ush is the naturalsource or cocaine# 8urari is the natural source or curare and tuocurarine# 8pium is the natural sourceor morphine+ codeine and theaine#Page reference:.3>a# Calaar ean# Coca ushc# 8urarid# 8pium

Type: multiple choice questionTitle:Chapter 19 Question 6161) Physosti"mine is a natural product !hich inhiits the acetylcholinesterase en?yme#

$hich o the ollo!in" "roups is not important to the compound=s acti%ity'Feedback:he urethane "roup is crucial to the dru"=s mechanism o action# he aromatic rin" is thou"htto act as a "ood lea%in" "roup# he pyrrolidine nitro"en is ionised and mimics the c# he anilino nitro"end# he pyrrolidine nitro"en

Type: multiple choice questionTitle:Chapter 19 Question 6464) Physosti"mine is a natural product !hich inhiits the acetylcholinesterase en?yme#



16/41


$hich portion o the molecule reacts !ith serine in the acti%e site and produces a stale intermediate!hich resists hydrolysis'Feedback:*erine acts as a nucleophile and interacts !ith the urethane "roup o physosti"mine# Anucleophilic sustitution reaction takes place on the urethane+ resultin" in caramoylation o the serineresidue#Page reference:.6>a# he urethane "roup# he aromatic rin"c# he anilino nitro"end# he pyrrolidine nitro"en

Type: multiple choice questionTitle:Chapter 19 Question 6363) Physosti"mine is a natural product !hich inhiits the acetylcholinesterase en?yme# A portion o themolecule reacts !ith serine in the acti%e site and produces a stale intermediate !hich resists hydrolysis#

$hy does this intermediate resist hydrolysis'Feedback:*ince the caronyl "roup is less reacti%e to nucleophiles+ the urethane cannot e hydrolysedy !ater and so the moiety transerred rom physosti"mine remains ound to serine#Page reference:.6-..

a# he moiety !hich is transerred acts as a steric shield and pre%ents !ater enterin" the acti%e site## he moiety !hich is transerred under"oes a urther alkylation reaction !ith a lysine residue#>c# he moiety !hich is transerred contains nitro"en !hich eeds electrons into the caronyl "roup andmakes it less reacti%e to nucleophiles#d# he moiety !hich is transerred is hydrophoic and repels !ater#

Type: matching questionTitle:Chapter 19 - Question 6666) he ollo!in" structures are analo"ues o physosti"mine C)



17/41


(ame the structures A and 2#Feedback:Miotine and neosti"mine are simpliied analo"ues o physosti"mine# Pyridosti"mine is anothersimpliied analo"ue o physosti"mine#Page reference:..a# A Miotine# 2 (eosti"mine

Type: multiple choice questionTitle:Chapter 19 Question 6.6.) he ollo!in" structures are analo"ues o o physosti"mine C)

$hat dru" strate"y has principally een used in the desi"n o the ao%e structures'Feedback:he tricyclic system has een replaced !ith a sin"le aromatic rin" and so these are simpliiedanalo"ues#

Page reference:..a# i"idiication



18/41


# Conormational lockin"c# 5tension>d# *impliication

Type: multiple choice questionTitle:Chapter 19 Question 6/

6/) he ollo!in" structures are analo"ues o physosti"mine C)

*tructure 2 is less susceptile to chemical hydrolysis than structure A# $hich eature is responsile orthis'Feedback:he dimethylamino "roup hinders the t!o possile mechanisms o hydrolysis#Page reference:..a# he urethane "roup># he dimethylamino "roupc# he aromatic rin"d# he


19/41


*tructure 2 is less susceptile to chemical hydrolysis than structure A# *tructure 2 is ree o C(* sideeects unlike structure A# $hich eature is responsile or this'Feedback:he


20/41


Feedback:he hydroyl "roup o serine acts as a nucleophile and reacts !ith the ner%e "as to ecomephosphorylated#Page reference:.@a# hreonine# ;istidine>c# *erine

d# Aspartic acid

Type: multiple choice questionTitle:Chapter 19 Question .0.0) 5cothiopate is used in medicine#

$hat is the a"ent used or clinically'Feedback:5cothiopate is an or"anophosphate !hich has een used to treat "laucoma and tar"ets theacetylcholinesterase en?yme# (euromuscular lockers and dru"s used to treat myasthenia "ra%is tar"et

choliner"ic receptors and not the acetylchoinesterase en?yme# *e%eral dru"s used in the treatment oAl?heimers disease tar"et the acetylcholinesterase en?yme includin" or"anophosphates+ ut ecothiopatehas not een used or this prupose#Page reference:.@a# Myasthenia "ra%is# Al?heimer=s disease>c# laucomad# (euromuscular lockade

Type: multiple choice questionTitle:Chapter 19 Question .1.1) 5cothiopate is used in medicine#

$hat is the main purpose o the


21/41


Page reference:.@-.>a# 8idati%e desulurisation# educti%e desulurisationc# ;ydrolysis o the thiophosphated# eduction o the nitro "roup

Type: multiple choice questionTitle:Chapter 19 Question .3.3) Parathion had an important commercial use as an insecticide#

espite the relationship o the ao%e structure to ner%e "ases+ it is relati%ely sae to mammals# $hy'Feedback:Parathion is relati%ely harmless in mammals and is metaolised in a dierent !ay rom themetaolic route in insects# I the compound wasmetaolised to the acti%e a"ent in mammals it !ould eas atal as the ner%e "ases#

Page reference:.a# 5posure to the dru" is only likely to result in skin contact# he metaolic en?yme rec# he metaolic en?yme re


22/41


Feedback:he correct ans!er is that it mimis the # It mimics the


23/41


It interacts !ith a receptor on the tar"et cell or the ner%e# A synapse is the small "ap that eists et!een t!oner%es+ or et!een one ner%e and a tar"et cell#Page reference:/9>a# It is an a"ent !hich inds to a receptor indin" site and acti%ates the receptor## It is an a"ent !hich inds to a receptor indin" site ut does not acti%ate it# 2y indin"+ it locks thenatural messen"er rom indin"#

c# It is a chemical !hich is released rom the end o a ner%e and acts as a chemical messen"er#d# It is a small "ap that eists et!een t!o ner%es+ or et!een one ner%e and a tar"et cell#

Type: multiple choice questionTitle:Chapter 19- Question .9.9) $hat is a synapse'Feedback:An a"onist is an a"ent !hich inds to a receptor and acti%ates it# An anta"onist is an a"ent !hich indsto a receptor ut does not acti%ate it# 2y indin"+ it pre%ents the natural li"and rom indin"# A neurotransmitter is achemical !hich is released rom the end o a ner%e and acts as a chemical messen"er# It interacts !ith a receptor onthe tar"et cell or the ner%e# A synapse is the small "ap that eists et!een t!o ner%es+ or et!een one ner%e and atar"et cell#Page reference:./0-./3a# It is an a"ent !hich inds to a receptor indin" site and acti%ates the receptor #

# It is an a"ent !hich inds to a receptor indin" site ut does not acti%ate it# 2y indin"+ it locks thenatural messen"er rom indin"#c# It is a chemical !hich is released rom the end o a ner%e and acts as a chemical messen"er#>d# It is a small "ap that eists et!een t!o ner%es+ or et!een one ner%e and a tar"et cell#

Type: multiple choice questionTitle:Chapter 19- Question /0/0) $hat is a neurotransmitter'Feedback:An a"onist is an a"ent !hich inds to a receptor and acti%ates it# An anta"onist is an a"ent !hichinds to a receptor ut does not acti%ate it# 2y indin"+ it pre%ents the natural li"and rom indin"# Aneurotransmitter is a chemical !hich is released rom the end o a ner%e and acts as a chemical messen"er#It interacts !ith a receptor on the tar"et cell or the ner%e# A synapse is the small "ap that eists et!een t!oner%es+ or et!een one ner%e and a tar"et cell#

Page reference:./0-./1a# It is an a"ent !hich inds to a receptor indin" site and acti%ates the receptor## It is an a"ent !hich inds to a receptor indin" site ut does not acti%ate it# 2y indin"+ it locks thenatural messen"er rom indin"#>c# It is a chemical !hich is released rom the end o a ner%e and acts as a chemical messen"er#d# It is a small "ap that eists et!een t!o ner%es+ or et!een one ner%e and a tar"et cell#

Type: multiple choice questionTitle:Chapter 19- Question /1/1) $hat is an anta"onist'Feedback:An a"onist is an a"ent !hich inds to a receptor and acti%ates it# An anta"onist is an a"ent !hich indsto a receptor ut does not acti%ate it# 2y indin"+ it pre%ents the natural li"and rom indin"# A neurotransmitter is achemical !hich is released rom the end o a ner%e and acts as a chemical messen"er# It interacts !ith a receptor on

the tar"et cell or the ner%e# A synapse is the small "ap that eists et!een t!o ner%es+ or et!een one ner%e and atar"et cell#Page reference:/9a# It is an a"ent !hich inds to a receptor indin" site and acti%ates the receptor#># It is an a"ent !hich inds to a receptor indin" site ut does not acti%ate it# 2y indin"+ it locks thenatural messen"er rom indin"#c# It is a chemical !hich is released rom the end o a ner%e and acts as a chemical messen"er#d# It is a small "ap that eists et!een t!o ner%es+ or et!een one ner%e and a tar"et cell#

Type: multiple choice questionTitle:Chapter 19- Question /4/4) $hat sort o interaction does the ester o acetylcholine ha%e !ith the indin" site o choliner"icreceptors'



24/41


Feedback:he acyl methyl "roup its a hydrophoic pocket and interacts y %an der $aals interactions# he oy"enatoms o the ester ser%e as hydro"en ond acceptors to aspara"ine /1@ in the indin" site# he


25/41


has a positi%e char"e and orms an ionic ond to aspartate 311# !o o the three N-methyl "roups it hydrophoicpockets and interact y %an der $aals interactions#Page reference:./.-./@a# Ionic interactions# ;ydro"en ondin" as a hydro"en ond acceptorc# ;ydro"en ondin" as a hydro"en ond donor

>d# Dan der $aals interactions

Type: multiple choice questionTitle:Chapter 19- Question /./.) $hat sort o interaction does aspartic acid 311 ha%e !ith acetylcholine in the indin" site o choliner"icreceptors'Feedback:Aspartic acid 311 is ionised and is present in the indin" site as a ne"ati%ely char"ed aspartate ion#Page reference:./.-./@>a# Ionic# Dan der $aalsc# ;ydro"en ondin" as a hydro"en ond acceptord# ;ydro"en ondin" as a hydro"en ond donor

Type: multiple choice questionTitle:Chapter 19- Question ////) $hich part o acetylcholine does Asp311 interact !ith in the choliner"ic indin" site'

Feedback:Asp311 contains a ne"ati%ely char"ed caroylate "roup !hich can orm an ionic interaction !iththe positi%ely char"ed c# he


26/41


Feedback:Aspara"ine /1@ interacts !ith the ester "roup y means o hydro"en ondin"#Page reference:./.-./@a# he acyl methyl "roup># he esterc# he c# 3d# 6

Type: multiple choice questionTitle:Chapter 19- Question @0@0) *e%eral aromatic amino acid residues present in the choliner"ic indin" site are thou"ht to interact !ith the


27/41


>c# It is not orally acti%ed# It is metaolically stale

Type: matching questionTitle:Chapter 19 - Question @4@4) Identiy the ollo!in" structures

Feedback:Compared to acetylcholine+ methacholine contains an etra methyl sustituent on the 4-C chainlinkin" the ester and c# *tructure Cd# *tructure

Type: multiple choice questionTitle:Chapter 19- Question @6@6) he ollo!in" structure is the choliner"ic a"onist ethanechol# $hich portion o the molecule is present

as a steric shield'

Feedback:he ester "roup is susceptile to acid and en?yme catalysed hydrolysis# he methyl "roup acts as asteric shield to incomin" nucleophiles#Page reference:./9a# roup A

# roup 2>c# roup C



28/41


d# roup

Type: multiple choice questionTitle:Chapter 19- Question @.@.) he ollo!in" structure is the choliner"ic a"onist ethanechol# $hich portion o the molecule stailisesthe molecule y electronic actors'

Feedback:he ester "roup is susceptile to acid and en?yme catalysed hydrolysis# he lone pair o the amino"roup interacts !ith the ester caronyl "roup and lo!ers its reacti%ity to nucleophiles# he amino "roup isapproimately the same si?e as the ori"inal methyl "roup and so it cannot act as a steric shield# It occupies the samehydrophoic pocket occupied y the methyl "roup+ ut is unale to interact y %an der $aals interactions since it is apolar "roup#

Page reference:./9>a# roup A# roup 2c# roup Cd# roup

Type: multiple choice questionTitle:Chapter 19- Question @/@/) $hich o the ollo!in" is not a clinical use or a muscarinic a"onist'Feedback:Muscarinic a"onists can e used to =s!itch on= the "astrointestinal and urinary tracts ater sur"ery# heyare not used to =s!itch them o=#Page reference:./9a# reatment o "laucoma

># =*!itchin" o= the urinary tract prior to sur"eryc# =*!itchin" on= the "astrointestinal tract tract ater sur"eryd# ecreasin" heart muscle acti%ity in certain heart deects

Type: matching questionTitle:Chapter 19 - Question @@@@) Identiy the ollo!in" a"ents#

Feedback:All the a"ents stated are muscarinic a"onists#Page reference:./9-.@0a# 8otremorine A"ent C# Muscarine A"ent Ac# Arecoline A"ent d# Pilocarpine A"ent 2

Type: multiple choice questionTitle:Chapter 19- Question @

@) $hich o the ollo!in" statements re"ardin" pilocarpine is true'



29/41


Feedback:Pilocarpine is a muscarinic a"onist and is used in the treatment o "laucoma# he statement =it islikely to e protonated !hen it interacts !ith the nicotinic receptor= is correct+ ecept or the act that it is themuscarinic receptor that is in%ol%ed#Page reference:./9-.@0a# It is a nicotinic a"onist## It is used in the treatment o myasthenia "ra%is#c# It is likely to e protonated !hen it interacts !ith the nicotinic receptor#>d# It can adopt a conormation !here the separation et!een nitro"en and oy"en is 6#6A#

Type: matching questionTitle:Chapter 19 - Question @9@9) Identiy the ollo!in" structures

Feedback:Atropine+ ;yoscine and amprotropine are muscarinic anta"onists# Atropine and hyoscine areclosely related structures deri%ed rom natural sources# Amprotropine is a synthetic structure !hich !asde%eloped as a simpliied analo"ue o these natural products# Arecoline is a synthetic compound !hich actsas a muscarinic a"onist and is not related to the pre%ious three compounds#Page reference:.@0-.@4a# ;yoscine *tructure 2# Arecoline *tructure c# Atropine *tructure Ad# Amprotropine *tructure C

Type: multiple choice questionTitle:Chapter 19- Question 0

0) $hich o the ollo!in" structures is not a muscarinic anta"onist'

Feedback:*tructures A-C are atropine+ hysocine and amprotropine+ all o !hich are muscarinic anta"onists#*tructure is arecoline !hich is a muscarinic a"onist#

Page reference:.@0-.@4a# *tructure A# *tructure 2



30/41


c# *tructure C>d# *tructure

Type: multiple choice questionTitle:Chapter 19- Question 11) $hich o the ollo!in" structures is a simpliied analo"ue o atropine'

Feedback:*tructures A- are atropine+ hysocine+ amprotropine and arecoline# *tructures A-C aremuscarinic anta"onists !hile arecoline is a muscarinic a"onist# Amptotropine is a simpliied analo"ue oatropine#Page reference:.@0-.@4

a# *tructure A# *tructure 2>c# *tructure Cd# *tructure

Type: matching questionTitle:Chapter 19 - Question 44) Identiy the ollo!in" structures

Feedback:uocurarine is a natural product !hich is the lead compound or neuromuscular lockers#ecamethonium and suamethonium are hi"hly simpliied analo"ues containin" the t!o


31/41


Feedback:he a"ents A- are tuocurarine+ pancuronium+ decamethonium and suamethonium# hey are allnicotinic anta"onists !hich are used as neuromuscular lockers#Page reference:[email protected].@@a# Cardio%ascular medicine># (euromuscular lockersc# Anti-asthmaticsd# Anal"esics

Type: multiple choice questionTitle:Chapter 19- Question 66) he ollo!in" structure is tuocurarine# $hich o the ollo!in" statements is alse'

Feedback:he distance et!een the t!o


32/41


$hich o the ao%e structures contains a steroid skeleton as a spacer'Feedback:*tructure 2 is pancuronium# the steroid skeleton allo!s the # *tructure 2c# *tructure C

d# *tructure

Type: matching questionTitle:Chapter 19 - Question //) Identiy the ollo!in" structures#

Feedback:uocurarine is a natural product !hich is the lead compound or neuromuscular lockers#ecamethonium and suamethonium are hi"hly simpliied analo"ues containin" the t!o


33/41


Feedback:*tructure A is atracurium !hich is set up or a ;oman elimination# he otherstructures 2-) are pancuronium+ decamethonium and suamethonium respecti%ely#Page reference:.@@-.@>a# *tructure A# *tructure 2

c# *tructure Cd# *tructure

Type: multiple choice questionTitle:Chapter 19- Question ) $hich o the ollo!in" structures does not contain the skeleton o acetylcholine !ithin its structure'

Feedback:ecamethonium does not contain an ester separated y t!o carons rom a


34/41


Feedback:ecamethonium does not contain an ester "roup and is not susceptile to esterases# he other structuresdo# *tructures A+ 2 and are atracurium+ pancuronium+ and suamethonium respecti%ely#Page reference:.@/-.@a# *tructure A# *tructure 2

>c# *tructure Cd# *tructure

Type: multiple choice questionTitle:Chapter 19- Question 9090) $hich o the ollo!in" statements concernin" the nicotinic receptor is true'Feedback:he nicotinic receptor is an ion channel or sodium ions# It contains . protein suunits+ t!o o!hich are identical# here are t!o choliner"ic indin" sites per ion channel# &inally+ the channel is open!hen acetylcholine is ound#

he nicotinic receptor is an ion channel or sodium ions#

Page reference:[email protected]

a# It is an ion channel or potassium ions## It contains i%e protein suunits+ three o !hich are identical#>c# here are t!o choliner"ic indin" sites per ion channel#d# $hen acetylcholine is ound the channel is shut#

Type: multiple choice questionTitle:Chapter 19- Question 9194) $hich o the ollo!in" statements concernin" the muscarinic receptor is alse'Feedback:It is too road a statement to say that si"nal transduction in%ol%es the secondary messen"er IP3#

It is certainly true or the muscarinic sutypes m1+ m3and m.# ;o!e%er+ the si"nal transduction process orthe sutypes m4and m6in%ol%e cyclic AMP#Page reference:.0a# It is a -protein coupled receptor#

# here are i%e sutypes#>c# *i"nal transduction in%ol%es the secondary messen"er IP3#d# Back o M1acti%ity is thou"ht to e associated !ith dementia#

Type: multiple choice questionTitle:Chapter 19- Question 9494) he ollo!in" dia"ram sho!s the irst part o the mechanism y !hich acetylcholine is inacti%ated yacetylcholinesterase# 8ne o the arro!s in the mechanism is incorrect# $hich one'



35/41


Feedback:he arro! or 2 is pointin" the !ron" !ay# Mechanism arro!s should point rom a source o t!o electronsand point to !here these electrons are "oin"# 8y"en=s lone pair o electrons is ein" used to orm a ond to the

hydro"en on histidine# hereore+ the arro! should point rom the lone pair to the hydro"en#Page reference:.4-.3a# A># 2c# Cd#

Type: multiple choice questionTitle:Chapter 19- Question 9393) he ollo!in" dia"ram sho!s the second part o the mechanism y !hich acetylcholine is inacti%ated yacetylcholinesterase# 8ne o the arro!s in the mechanism is incorrect# $hich one'

Feedback:Arro! A is dra!n incorrectly# he lone pair o electrons on the !ater oy"en is ein" used to orm a ondto the caronyl "roup# he arro! su""ests that the electrons are comin" rom the 8-; ond#Page reference:.4-.3>a# A# 2c# Cd#




36/41


37/41


Feedback:*arin is an or"anophosphate ner%e "as# ylos is a similar a"ent !ith a sli"htly dierentstructure# 5cothiopate is an or"anophosphate a"ent !hich is used in medicine# Parathion is an insecticide#Page reference:./-.a# Parathion *tructure C# ylos *tructure 2c# *arin *tructure Ad# 5cothiopate *tructure

Type: multiple choice questionTitle:Chapter 19- Question 99) $hat kind o compounds are the ollo!in"'

Feedback:*tructures A- are sarin+ dylos+ parathion and ecothiopate respecti%ely#Page reference:./-.a# 8r"anophosphates># 8r"anophosphonatesc# 8r"anotoins

d# 8r"anophosphites

Type: multiple choice questionTitle:Chapter 19- Question 9999) $hat is the tar"et or the ollo!in" compounds'

Feedback:*tructures A- are sarin+ dylos+ parathion and ecothiopate respecti%ely#Page reference:./-.>a# Acetylcholinesterase en?yme# Muscarinic receptorc# (icotinic receptord# Choline acetyltranserase

Type: multiple choice questionTitle:Chapter 19- Question 100100) $hich o the ollo!in" compounds has een used as an insecticide'



38/41


Feedback:*tructures A- are sarin+ dylos+ parathion and ecothiopate respecti%ely# *arin is an or"anophosphatener%e "as# ylos is a similar a"ent !ith a sli"htly dierent structure# 5cothiopate is an or"anophosphate a"ent !hichis used in medicine# Parathion is an insecticide#Page reference:[email protected]# *tructure A# *tructure 2>c# *tructure Cd# *tructure

Type: multiple choice questionTitle:Chapter 19- Question 101101) $hich o the ollo!in" compounds has een used as a medicine'

Feedback:*tructures A- are sarin+ dylos+ parathion and ecothiopate respecti%ely# *arin is an or"anophosphatener%e "as# ylos is a similar a"ent !ith a sli"htly dierent structure# 5cothiopate is an or"anophosphate a"ent !hichis used in medicine# Parathion is an insecticide#Page reference:[email protected]# *tructure A

# *tructure 2>c# *tructure Cd# *tructure

Type: multiple choice questionTitle:Chapter 19- Question 104104) he ner%e "ases are irre%ersile inhiitors o the acetylcholinesterase en?yme and react !ith a serineresidue in the acti%e site# $hat kind o reaction takes place on the serine residue'Feedback:he hydroyl "roup o serine acts as a nucleophile and reacts !ith the ner%e "as to ecomephosphorylated#Page reference:.@a# eduction# 8idation

>c# Phosphorylationd# 5steriication




39/41


Feedback:acrine+ malathion+ and sarin are all anticholinesterases# Malathion is an or"anophosphorusa"ent used as an insecticide# *arin is an or"anophosphate !hich has een used as a ner%e "as# acrine isa tricyclic system used in the treatment o Al?heimer=s disease# Pralidoime is used as an antidote toor"anophosphate poisonin"Page reference:./-.90a# acrine *tructure 2

# Malathion *tructure c# Pralidoime *tructure Ad# *arin *tructure C

Type: multiple choice questionTitle:Chapter 19- Question 106106) $hich o the ollo!in" has een used as a =smart dru"='

Feedback:*tructure A is pralidoime !hich is used as an antidote to or"anophosphate poisonin"# *tructure2 is tacrine !hich has een used in the treatment o Al?heimer=s disease# *tructure C is sarin !hich is aner%e "as# *tructure is malathion !hich has een used as an insecticide#Page reference:.9-.90a# *tructure A># *tructure 2c# *tructure Cd# *tructure


Title:Chapter 19- Question 10.10.) $hich o the ollo!in" has een used as an antidote or or"anophosphate poisonin"'

Feedback:*tructure A is pralidoime !hich is used as an antidote to or"anophosphate poisonin"# *tructure2 is tacrine !hich has een used in the treatment o Al?heimer=s disease# *tructure C is sarin !hich is aner%e "as# *tructure is malathion !hich has een used as an insecticide#

Page reference:.-.9>a# *tructure A# *tructure 2c# *tructure Cd# *tructure

Type: multiple choice questionTitle:Chapter 19- Question 10/10/) $hich o the ollo!in" has een used as a ner%e "as'



40/41


Feedback:*tructure A is pralidoime !hich is used as an antidote to or"anophosphate poisonin"# *tructure2 is tacrine !hich has een used in the treatment o Al?heimer=s disease# *tructure C is sarin !hich is aner%e "as# *tructure is malathion !hich has een used as an insecticide#Page reference:.@a# *tructure A# *tructure 2>c# *tructure Cd# *tructure

Type: multiple choice questionTitle:Chapter 19- Question 10@10@) $hich o the ollo!in" has een used as an insecticide'

Feedback:*tructure A is pralidoime !hich is used as an antidote to or"anophosphate poisonin"# *tructure2 is tacrine !hich has een used in the treatment o Al?heimer=s disease# *tructure C is sarin !hich is aner%e "as# *tructure is malathion !hich has een used as an insecticide#Page reference:.@-.

a# *tructure A# *tructure 2c# *tructure C>d# *tructure

Type: multiple choice questionTitle:Chapter 19- Question 1010) $hat sort o a"ents are the ollo!in" structures'

Feedback:he a"ents A- are tuocurarine+ pancuronium+ decamethonium and suamethonium# hey are allnicotinic anta"onists !hich are used as neuromuscular lockers#Page reference:[email protected].@@a# Muscarinic a"onists

# Muscarinic anta"onistsc# (icotinic a"onists



41/41


>d# (icotinic anta"onists

Patrick Tb Ch19

Documents

Transcript of Patrick Tb Ch19