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MUSCARINIC AND NICOTINIC CHOLINOCEPTORS

AGONISTS AND ANTAGONISTS

Drugs on cardiovascular sys!" in vivo

Pr!#ar!d $y Mar%n&ov' () C*l'd!& () +al*ousov' H, using PC #rogra":

I,E,Hug*!s H!ar ra! and $lood #r!ssur! -Univ!rsiy o. L!!ds) England/

InroducionDemonstrations of the properties of drugs which affect the autonomic nervous system, heart and blood

vessels can be performed on conscious or anaesthetised animals. Recordings of heart rate and

blood pressure of animals (usually a dog, cat or rat) can easily be made and students gain

immensely from working with such in vivopreparations. Unfortunately, such eperiments are

epensive, are very time consuming and use many animals. !herefore, this simulationof theseeperiments may enable some of the teeching ob"ectives for which such preparations are used to

be achieved without the use of animals and may also be usefull to suppliment #hands$on#

eperiments.

0, Progra" o#!raion!he program is basically self$eplanatory and menu driven. !he user must select a particular drug or

procedure from menu% the re&uired dose (entirely in the hand of the user) is then entered.

'ppropriate blood pressure and heart rate records are then displayed on screen. !he menu in then

redisplayed and the net drug or procedure can be selected. !he user can leave the program

completely from the menu at any time.

ow to start: ardiovascular pharmacology*ress: + for colour displey

+ for dose in g-kg

+ for blood pressure in mmg

for output on R//0

1 for no pretreatment

02R3'4 *R/*'R'!520, 4ist of available drugs appears$ basic menu

1, P*ar"acological su""ary2utlined below are the ma"or actions shown by the drugs available. !he presence of reflees may

modify the effects observed. 0ote that at high dose levels additional effects will become apparent.

6ollow the instructions generated by the program:

2, Drugs in us!Ta$,0, Agoniss on c*olinoc!#ors

'cetylcholine stimulates muscarinic cholinoceptorsand evokes a depressor response along

with negative chronotropic and inotropic effects. A *ig*!r dos!s

stimulant effects at nicotinic cholinoceptorsmay be seen with conse&uential

release of catecholamines

0eostigmine 'n anticholinesterase ('/) agent

Ta$,1, Anagoniss on c*olinoc!#ors

'tropine ' competitive blocker on muscarinic cholinoceptors

ompare effects of atropine +7 a +777 g-kg on ' dose$response curve

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E3!rcis!s

E3#!ri"!n 04 E..!cs o. ac!ylc*olin! -ACH/ on $lood #r!ssur! and *!ar ra!

5n"ect intermittent doses of ACH (press 8) in g-kg $ tab.1 and register systolic-diastolic blood

pressure (9*-D9*) and heart rate.

Ta$, 2,Sysolic5diasolic $lood #r!ssur! H!ar ra!

5nitial values

ACH 6g5&g

7.77+

7.7+

7.+

+

+7

+77

+777

ave you registered both muscarinic and nicotinic effects

!erminate the preparation (press 17). ontinue ;.

onstruct the dose$response curve of acetylcholine (DR') < using 9* (tab. 1, 6ig. +).

E3#!ri"!n 14 E..!cs o. n!osig"in! and ACH on $lood #r!ssur! and *!ar ra!

'dministern!osig"in!(press =>), =77g-kg then ACH(press 8) at increasing doses $ tab.>.Ta$, 7,

Sysolic5diasolic $lood #r!ssur! H!ar ra!

5nitial values

N!osig"in! 188 6g5&g/ffects of neostigmine

9 ACH 6g5&g

7.77+

7.7+

7.+

+

+7

+77

ave you registered both muscarinic and nicotinic effects

!erminate the preparation (17). ontinue ;.onstruct dose$response curve (9*) of acetylcholine (DR') in presence of neostigmine.

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E3#!ri"!n 24 E..!cs o. aro#in! and ACH on $lood #r!ssur! and *!ar ra!

'dminister aro#in! (press +?), 086g5&gthen use ACH(press 8) at increasing doses $ tab.@.

Ta$, :,

Sysolic 5diasolic $lood #r!ssur! H!ar ra!

5nitial valueAro#in! 08 6g5&g

/ffects of atropine

9ACH6g5&g

+.7

+7

+77

+777

+7777

ave you registered both muscarinic and nicotinic effects

!erminate the preparation. ontinue ;.

onstruct DR'(9*) in presence of atropine (6ig.+). ompare DR'with that in eperiment +.

E3#!ri"!n 74 E..!cs o. aro#in! and ACH on $lood #r!ssur! and *!ar ra!

'dminister aro#in! (press +?) 08886g5&gthen use ACH(press 8) at increasing doses

(tab.?).

Ta$, ;,

Sysolic 5diasolic $lood #r!ssur! H!ar ra!

5nitial value

Aro#in! 0888 6g5&g

/ffects of atropine

9 ACH 6g5&g

+7

+77

+777

+7777

ave you registered both muscarinic and nicotinic effects

!erminate the preparation. ontinue ;.

onstruct DR'(9*) in presence of atropine (6ig.+). ompare DR'with that in eperiment +

(6ig.+).

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S!l!c "uli#l! r!c!#or su$y#!s0eurotransmitters have multiple receptor subtypes with which to interact. 5t is as though the

neurotransmitter $ a master keycapable of unlocking each of the multiple locks of receptors subtypes.

Drugs can be made that mimic the neurotransmitter, but many are more selective than the natural

neurotransmitter, thus defining a pharmacological subtype at which they specifically interact.

!his figure shows a neurotransmitter capable of binding to several different receptor subtypes(i.e.master key). 'lso shown are several different drugs on a key chain. /ach of these drugs is

selective for a single subtype of the neurotransmitter receptors.

5ndicate the cholinoceptor subtype stimulated (s) or blocked (b) if some drug is administered i.v.

(intravenously).

3+$31 muscarinic cholinoceptors,

03 nicotinic cholinoceptors in skeletal muscle 00 in the ganglia 00 in the central nevrous system

Conclusions$simulation b$blockade d$direct i$indirect

3+ 3= 31 03 00 00' neostigmine

9 pilocarpine

atropine

D tolterodine

/ nicotine

ompare the neurotransmitter with drugs influencingparticular receptors subtypesand

indicate which determines pharmacodynamic property: