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I read in Tortora and Derrickson that :

Enkephelins are 200 times powerful than morphine in their analgesic effects.

I wonder how exactly researchers arrive at a number (like 200 here). I also want to know what exactly is meant by "powerful".

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I don't know if it is applicable for the drugs under discussion, but many a times, quantifiable effects are used to compare, for example, the amount of medicine required to block gastric proton pumps to such an extent that a predetermined acidity is maintained in stomach is used. Now different drugs will require different amounts and hence can be quantitatively compared. – Satwik Pasani Jan 3 '14 at 14:24
up vote 4 down vote accepted

In general, there is no universal way to quantify the effect of a drug; the quantification procedure depends crucially on what effect the drug is supposed to have. For example, if the drug is supposed to decrease blood thickness, then a measure of the drug's efficacy is a measurement of change in blood thickness upon application of a given concentration of drug. So I'll focus on the case of analgesics, since that's the context of your original question.

While I can't say for sure how this particular quantity was measured, it appears that the effect of analgesics like morphine or enkephalins is measured by direct measurements of pain under different administered concentrations of drug. This can be done in animal or human studies. In animal studies, varying concentrations of a drug are administered, and then the response of the animal to different pain stimuli is recorded. One common example of a pain measurement is a hot plate, where the animal's foot is placed on a hot plate and the time until it tries to remove its foot is measured.

These studies can also be done in humans. In this study (1), the effect of a particular drug was measured by different tests, including

  • electrical shocks of increasing intensity; maximum intensity of pain subject wanted to endure was measured.
  • pressure applied to the finger: maximum pressure subject wanted to endure was measured.
  • heat applied to the forearm (maximum tolerable temperature measured)
  • dominant hand immersed in ice water for up to 2 minutes. Subjects continually reported level of pain on a 0-10 scale, sum of all pain levels over course of experiment was used as measurement of total pain endured.
  • Tourniquet applied to cut off blood supply for up to 2 minutes, pain measured in same way as above.

If these pain measurements are recorded when the patient has different levels of the drug in their system, then comparing drug effects amounts to identifying the concentration of drug at which a particular pain response is achieved. In other words

Drug A is X times more powerful than drug B if drug A causes the same effect on pain response (measured in some way like the ones measured before) as drug B at X times lower concentration.

As a side note, the initial thought I had was that this might be measured by quantifying the receptor-ligand affinity of the various drugs for the pain receptors (opioid receptors) in the nervous system. In that situation, saying that drug A was 200 times more powerful than drug B would amount to saying that A's affinity (or Kd) for a particular receptor was 200 times greater than B. Or something along those lines (see the Wikipedia article on receptor-ligand interactions). That would be a 'universal' way to measure drug efficacies, since a large number of drugs work by blocking certain receptors in the brain. But biology is too complicated to permit a straightforward relationship between binding affinity and perceived drug effect. At least, not yet!

References and Further Reading

(1): Luginbuhl M et al (2001). Comparison of Five Experimental Pain Tests to Measure Analgesic Effects of Alfentanil. Anesthesiology 95:22-29

(2): Jackson H. (1952) The effect of analgesic drugs on the sensation of thermal pain in man. Br. J. Pharmacol Chemother. 7(2): 204–214.

(3):Estrup Olesen A et al. (2012). Pharmacological Reviews 64(3):722-779 Extensive review of this subject.

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