2018-03-19 12:34:18
Among the most powerful analgesics are opiates, a class to which the well-known morphine belongs, which is considered the first substance with pharmacological properties extracted from a plant, back in 1805.
Biomedical research has revealed that opioids are relatively simple molecules that bind to and act on other sensing molecules present on the surface of various cell types, including nerve cells. These detector molecules are called opioid receptors. Science has also revealed that these receptors have the mission of detecting, binding and generating a cellular reaction against natural opioids, that is, those manufactured by the body itself. Indeed, our body manufactures endogenous opioids, which are usually small proteins, such as the so-called endorphins, which have multiple regulatory functions in the nervous system.
All these actions depend on the binding of a specific opioid to one or several receptors, which are activated by this binding and trigger a series of biochemical mechanisms inside the cell that lead to the activation or inactivation of certain genes. By changing its running genes in this way, the cell changes its behavior accordingly.
The biggest problem in controlling the pharmacological activity of synthetic or purified plant opioids is that they generally bind to more than one receptor. It is not surprising when it is known that there are seventeen opioid receptors, although the main ones are only three, named with the Greek letters delta, kappa and mu. The binding of a particular opioid to a specific receptor is what generates the primary effect sought, generally reducing pain, but binding to other receptors also generates different secondary effects. Thus, we can use here again the old molecular analogy that opiates act as master keys that open various locks, a role that, in this case, corresponds to the opiate receptors.
It would therefore be important to be able to have more precise opioids, specific for only one of the receptors, the one on which it is most appropriate to act to achieve the sought analgesic effect.
To try to achieve this objective, researchers from the University of North Carolina have developed a new strategy that allows determining the three-dimensional structure of the kappa opiate receptor in its activated form. Previous research indicated that this receptor was the best candidate for developing pain relievers with fewer side effects.
Well, the knowledge of its structure in an active way (that is, when the key is inserted inside the lock) has now allowed us to know how the structure of a key should be that fits better in that lock than the keys we had. until now. With this knowledge, scientists have succeeded in synthesizing a new opiate molecule and have verified that it fits perfectly in the kappa receptor, but not in the other two main opiate receptors.
Until now, these works have been carried out with cells grown in the laboratory. The next step will be to evaluate the analgesic effects of this substance in animals. If successful, the molecule should be studied in clinical trials with patients.
Reference:
Che et al., Structure of the Nanobody-Stabilized Active State of the Kappa Opioid Receptor, Cell (2018),
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