Pharmacology Report: NS-009 Compound and Guinea Pig Ileum

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This report details a pharmacology experiment that investigated the effects of the test compound NS-009 on the contractility of a guinea pig's small intestine. The experiment utilized a simulation program to mimic real-life pharmacological trials, examining the interactions of agonists and antagonists with relevant receptors. Acetylcholine (Ach) was used as an agonist to stimulate contractions, while NS-009 was tested to understand its impact on the Ach-induced response. The results, illustrated through graphs, demonstrated that NS-009, when introduced with ACh, acted as a non-competitive antagonist, reducing contractility. The report also highlights the importance of receptor types, and the method and materials used in the experiment. The study aimed to understand the pharmacological mechanisms of action of NS-009 and its effect on smooth muscle function in the ileum, supported by references to relevant research in the field.
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Pharmacology 1
Pharmacology
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Pharmacology 2
Abstract
The simulation program was provided to the students with an objective to examine
pharmacological impacts of the actions in regards to selected test compound (NS-009) and the
impacts on the contractility of the sampled guinea-pig small intestine. The agonist and antagonist
elements were effectively tested in an aim to comprehend their unique features and connections
with their receptor kinds.
The provided software looked like an actual life experimental procedure and was
examines with agonist substance; acetylcholine (Ach). Initial studies done concluded several
sources of the receptor types linked with the guineas pig ileum making antagonist have
outstanding impacts in regards to contractility. However, the simulation was an operative device
in checking the impacts of varying and reinforced the experiment’s results.
Introduction
The simulated program pharmacological trials on the sampled guinea pig small intestine
was one of the effective item in comprehending the major methods and the difference between
the agonist which was starting the response with receptor and antagonist which on the other hand
inhibits the physiological impact of the other substance and their duty in connection with the
smooth muscle of the ileum of guinea pig (Muise et al., 2017). The smooth muscles of the guinea
pig are made up of contractile features which allow the reading to be noted through contractions
stirred by the muscle.
The main objective of the simulated experiment is to examine the pharmacological
implications of actions in a provided test compound NS-009 on the contractility of the sampled
ileum of the guinea pig following the procedure of drug evaluation. In addition, the ileum of the
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Pharmacology 3
guinea pig is important intestine components which have epithelial layers that have a role in the
uptake of water and nutrients (Amer et al., 2015). The present receptors in the ileum of the
guinea pig encompass histaminergic, cholinergic and serotonergic receptors (Muise et al., 2017).
The magnitude of the responses within each receptor will because of the varying receptors in the
ileum. Consequently, varying agonistic compounds will act on one or several receptors to induce
a needed response. Furthermore, contrary to the agonist, the antagonist substance will hinder the
response evoked by the agonist.
Method
Materials.
The simulated experiment was employed in combination with the software package; the
“pharmacological experiments on the sampled ileum of the Guinea pig” replication program.
The experiment setup of the sample which was 2cm in length was simulated by the software
package and suspended in a warm tyrode solution. Lever, organ bath and transducer was
employed in the investigation in an aim to suspend the tissues and also to respond to the
contractions and also the electrical signals from resulting movement s recorded by the
transducer. However, it was very necessary to use chart recorder meant for showing the signals,
the water jacket meant to ensure the consistent circulation of warm water to retain the
temperatures at 370C and different agonistic and antagonistic drugs which were needed in the
experiment.
Experiment set up
Ileum should be carefully sampled and appropriately suspended in a warm tyrode solution and
adequate handling should be done to reduce the contamination and soft tissues. Suspension of the
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Pharmacology 4
tissues in organ bath should be in such a way that its bottom end is fixed to a height which could
be maintained. The top part of the tissues should be put to sampled isotonic solution lever which
is linked to the transducer. The electrical signals conveyed to the graph was observed
subsequently to each and every contraction. The organ bath ought was maintained at 370C to
reduce any possible errors
Procedure
Before the experiment was done, there should be a full knowledge of agonistic and
antagonistic substances. There should be appropriate simulations done in order to comprehend
the maximum ceiling dose. The process can be attained by a restricted dose of agonist drug
applied to the ileum and progressively increasing the dose until the maximum reaction (ceiling
response) that an agonist can induce. The submaximal response of agonist should be selected and
reproduced it making sure to save the recording.
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Results
0 200 400 600 800 1000 1200
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
NS-009 alone
Dose of NS-009
Contractility
Figure 1 showing NS-009 alone
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Pharmacology 6
0 10 20 30 40 50 60 70 80 90
0
10
20
30
40
50
60
70
ACh alone
Dose of ACh
Contractility
Fig 2 showing ACh alone
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Pharmacology 7
0.5 1 1.5 2 2.5 3 3.5 4 4.5
0
2
4
6
8
10
12
14
16 ACh in the presence of NS-009 compound
Figure 3 showing ACh in the presence of NS-009 compound
Discussions
The experiment aimed at finding out the pharmacological effects and mechanism of
action of a certain test of the compound on the sampled guinea pig's ileum. In the graph at
figure 1, the test compound NS-009 has no impact on contractility of guinea pig ileum due to its
noncompetitive action. It has no any effect in the absence of the agonist and that is the reason
there is no increase or decrease in contractility
In graph 2 there were some agonist substances which were implemented to cause
contraction and for this case is acetylcholine;ACh (Viana et al., 2013). It is clear from the
contractions that the impacts of acetylcholine; a nicotinic receptor evoke and increases reactions
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and because it lacks a competitor in its receptors, the contractility increases rapidly (Syverud et
al., 2016).
In graph 3, when compound NS-009 is introduced to Ach it prevents its receptors
producing non-competitive antagonists of ACh, thus the contractility is reduced drastically.
(Badavi et al., 2013).The utilization of the agonist test compounds in the experiment had a big
role in starting the physiological response at a particular dose (Moreira and Dalley, 2015).
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Pharmacology 9
Reference list
Amer, M.I.M., Omar, O.H., Hamed, M.E.S. and Dahroug, E.G., 2015. Subendometrial blood
flow changes by 3-dimensional power Doppler ultrasound after hysteroscopic lysis of
severe intrauterine adhesions: preliminary study. Journal of minimally invasive
gynecology, 22(3), pp.495-500.
Badavi, M., Abedi, H. A., Sarkaki, A. R., & Dianat, M. (2013). Co-administration of grape seed
extract and exercise training improves endothelial dysfunction of coronary vascular bed
of stz-induced diabetic rats. Iranian Red Crescent Medical Journal, 15(10).
Moreira, F.A. and Dalley, J.W., 2015. Dopamine receptor partial agonists and
addiction. European journal of pharmacology, 752, pp.112-115.
Muise, E.D., Gandotra, N., Tackett, J.J., Bamdad, M.C. and Cowles, R.A., 2017. Distribution of
muscarinic acetylcholine receptor subtypes in the murine small intestine. Life
sciences, 169, pp.6-10
Syverud, B.C., VanDusen, K.W. and Larkin, L.M., 2016. Growth Factors for Skeletal Muscle
Tissue Engineering. Cells Tissues Organs, 202(3-4), pp.169-179.
Viana, T.G., AlmeidaSantos, A.F., Aguiar, D.C. and Moreira, F.A., 2013. Effects of
aripiprazole, an atypical antipsychotic, on the motor alterations induced by acute ethanol
administration in mice. Basic & clinical pharmacology & toxicology, 112(5), pp.319-324.
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