Agonist Potency

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Agonist Potency

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Abstract

The effectiveness of drugs in pharmacology is determined by using the recommended EC50 of varied agonists’ concentration. EC50 is the concentration of agonist that produces maximum response at 50%. This experiment was conducted with the primary objective of comparing the potency of BU007 and BU006 on the pig bladder’s muscarinic receptor. This was conducted by immersing the bladder tissues of the pig into krebs solution baths before being exposed to BU007 and BU006 drugs of different concentrations. It is after these that the values of the receptor occupancy and the EC50 values of these two drugs were determined through by calculating them. The result of this experiment showed that BU007 and BU006 had different EC50 concentrations of 95.63% and 97.76% respectively. Besides, the t-test for the mean contractile response to BU007 and BU006 showed no statistically significant differences. From these experimental results, it was established that since BU007 produced a relatively lower EC50 than BU006, it was worth concluding that BU007 is therefore more potent compared to BU006 that produced a higher concentration of EC50, as compared to BU006, an indication that BU007 drug attained half of the maximal response in the experiment with lower concentrations.

Introduction

A number of physiological processes are highly influenced by the receptors that are often activated in order to induce the signal cascades that further leads to the physiological responses. The receptors can also be inhibited in the patient to produce physiological responses by stopping the signal cascades from working. All the endogenous chemicals messengers that are found in the body (such as neurotransmitters or hormones) bind to these body receptors thereby instigating a physiological body response particularly on the body cells having these receptors (Rang, et al, 2007). It is this receptor that pharmacologists play with in altering the body physiological responses by using drugs with the ability to block or mimic the effects and threats caused by natural chemical messengers in the body. As outlined by pharmacologists, any drugs has two main features; efficacy that defines the degree of physiological response of the body after being initiated by the receptor chemical messengers with the ability to mimic. Secondly, drugs have the affinity that enables them to strongly bind to the receptors, an ability of the chemical messenger mimicking pharmaceutical drugs. The drug’s potency is the relationship that exists between the drug’s efficacy and the drug concentration, thus, representing the ability the messenger mimicking drugs to realize the highest level of efficacy possible with the lowest EC50 concentration possible.

From a pharmacological point of view, agonist represents drugs that enhance the receptors’ activities (those receptors that the agonist binds) so as to induce or facilitate a pharmacological reaction that is similar that showed when in its natural state. Notably, the agonist’s efficacy is more valued over its affinity. Unlike full agonists, partial agonists produce less response that is not as effective in enhancing the activities and operations of the body receptors. Contrary to agonists, antagonists are a group of pharmaceutical drugs that block or inhibit the normal activities and operations of the body receptors that they bind to, hence inhibiting any natural physiological response that would have been produced by the attacked receptors. As opposed to agonists where efficacy is of greater significance than affinity, antagonist drugs place value on affinity over efficacy that is always zero (Rang et al. 2007).

Different agonists imposed on a single receptor often produce different maximum responses, which is the highest possible response of the agonists. However, in pharmacology, the potent degree of drugs is determined by EC50 with different agonists’ concentrations. Pharmacologically, EC50 is defined as the agonist’s concentration level that produces 50% of maximal drug responses. According Rang et al. (2007), the differences in the EC50 concentration in different drugs is such that the agonist drug that produces 50% of the maximal response at the lowest concentration is considered more potent.

The drugs that were examined in this pharmacological experiment were both tissue bladder agonists and their potencies tested by the use of pig bladders. The pig bladder was used in this experimental given the fact that pig bladder have the M3 (type 3 muscarinic) receptors that also exist on the human bladder. Asserts Marieb & Hoehn (2010), the muscarinic receptors are presents on the walls and other soft parts of bladder muscles and hence stimulating muscle contraction of the body when bound by Ach (Acetylcholine). In particular, the bladder smooth muscles found in human contain M3 (70-80%) and M2 (20-30%) receptors (Choppin, 2002). The activation of M3 receptors results into a G-coupled protein and phospholipase initiated direct contraction. On the other hand, the activation of M2 receptors in the body tissues would result into indirect body contraction that takes place by inhibiting the activities of the receptors through G-protein and cationic current elicitation (Choppin, 2002; Mehdia et at, 2011). As earlier stated, the primary objective of this research experiment was to evaluate the differences in the potency of BU007 and BU006 on the muscarinic receptor tissues of the pig’s bladder.

Methods

This was done “As per Laboratory Protocol, BMED 13-217 Pharmacology, Pg.23-33, Agonist Potency, Bond University, 2012.

The data was analyzed using unpaired 2-tailed t-test.

 

Results

Part A: Individual Lab Report for BU006

Fig.1: Contractile Response (of the bladder tissue) plotted against BU006 Concentration at EC50 value.

From the above figure (Fig.1) it was evidenced that the BU006 had little effect on these tissues until the point where the concentration of the BU006 was 100ug/25ml with the corresponding maximum contractile response being 22. The simulation peak was realized at 10000ug/25ml BU concentration level. From fig.1, the EC50 for BU006 was on 800ug/25mil concentration level.

Molar EC50, pEC50 values and receptor accupancy for the BU006

EC50 into Molar Units:

EC50 for BU006 mass = 800 ug; molecular weight = 183g/mol

Moles = Mass (g) / Molar weight (g/mol)

Moles = 800ug/183g/mol

Moles = 8-4/183 = 1.334 x 10-6Mole

Recall, M = Moles / Vol.

Molarity (M) = 1.334 x 10-6/0.025 = 5.336 x 10-5M = 53.36 uM

Converting Molar EC50 to pEC50 value

EC50 Value = 53.36 uM = 53.36 x 10-6 M

pEC50 = -log (53.66 x 10-6) M

PEC50 = 4.271

Receptor occupancy for BU006 at EC50

Dissociation Constant (KD) for BU006 was at 10uM

Receptor Occupancy = 53.36uM / [10uM+53.36uM] = 0.8422 = 84.22%

The Molar Emax and Receptor Occupancy for the BU006

Converting Emax to Molar units:

Mass of Emax = 10mg and molecular weight = 183g/mol

Moles = 10000ug/[183g/mol] = 54.64 x 10-5 Moles

Molarity (M) = 54.64 x 10-5 /0.025

M = 21.86 x 10-3M

M = 21860 uM

Receptor Occupancy for BU006 at Emax

KD of BU006 was 10uM

Receptor Occupancy = 21860 / [10 +21860)

= 99.94%

Therefore, the space receptors have a value of 0.06%.

Fig.2: Contractile Response (of the bladder tissue) plotted against BU007 Concentration at EC50 value.

Part B: Combined Experimental Data for BU007 and BU006

Fig.3, contractile response against BU007 and BU006 drug concentration at EC50 values for both drugs.

Measurable effects were realized at 1000ug/25ml while the maximum value was noticed at 10000ug/25ml while the EC50 values fo.............


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