Opioids, their analogues

There is a huge number of new synthetic opiates and their analogues, they will be discussed in this article.

This group includes narcotic analgesics with a pronounced ability to alleviate or eliminate the feeling of pain.

Analgesic activity is manifested by substances with different chemical structures, and it is realized by various mechanisms. Modern analgesics are divided into two main groups: narcotic and non-narcotic. Narcotic analgesics, providing, as a rule, a strong analgesic effect, cause side effects, the main of which is the development of addiction (drug addiction). Non-narcotic analgesics act less strongly than narcotic, but do not cause drug dependence — drug addiction (see Non-narcotic analgesics, including nonsteroidal and other anti-inflammatory drugs).

Opioids are characterized by strong analgesic activity, which makes it possible to use them as highly effective painkillers in various fields of medicine, especially for injuries, surgical interventions, injuries, etc. and in diseases accompanied by severe pain (malignant neoplasms, myocardial infarction, etc.). Having a special effect on the central nervous system, opioids cause euphoria, a change in the emotional color of pain and a reaction to it. Their most significant drawback is the danger of the development of mental and physical dependence.

This group of analgesics include natural alkaloids (morphine, codeine) and synthetic compounds (trimeperidine, fentanyl, tramadol, nalbuphine, etc.). Most of the synthetic drugs obtained by the principle of modification of the molecule of morphine with the preservation of the elements of its structure or its simplification. By chemical modification of the morphine molecule, substances that are its antagonists (naloxone, naltrexone) were also obtained.

According to the severity of analgesic action and side effects, the drugs differ from each other, which is associated with the characteristics of their chemical structure and physicochemical properties and, accordingly, with the interaction with the receptors involved in the implementation of their pharmacological effects.

In the understanding of the neurochemical mechanisms of action of opioids, the discovery in the 70s of specific opiate receptors and their endogenous peptide ligands, enkephalins and endorphins, played an important role. Opiate receptors are concentrated mainly in the central nervous system, but are also found in peripheral organs and tissues. In the brain, opiate receptors are mainly found in structures that are directly related to the transmission and coding of pain signals. Depending on their sensitivity to different ligands, subopopulations are distinguished from the opiate receptors: 1- (mu), 2- (kappa), 3- (delta), 4- (sigma), 5- (epsilon), with different functional significance.

By the nature of interaction with opiate receptors, all opioidergic drugs are divided into:

– agonists (activate all types of receptors) – morphine, trimeperidine, tramadol, fentanyl, etc .;

– partial agonists (they activate predominantly mu receptors) – buprenorphine;

– antagonist agonists (activate kappa- and sigma- and block the mu- and delta-opiate receptors) – pentazocine, nalorphin (blocks mainly the mu-opiate receptors and is not used as an analgesic);

– antagonists (blocking all types of opiate receptors) – naloxone, naltrexone.

In the mechanism of opioid action, the inhibitory effect on the thalamic centers of pain sensitivity, which conduct pain impulses to the cerebral cortex, plays a role.

A number of opioids are used in medical practice. In addition to morphine, its prolonged dosage forms are created. A significant amount of synthetic highly active analgesics of this group (trimeperidine, fentanyl, buprenorphine, butorphanol, etc.) with high analgesic activity with varying degrees of “drug addiction potential” (ability to cause painful addiction) was also obtained.

In case of poisoning or overdose with narcotic analgesics, antagonists are used that block all types of opioid receptors (naloxone and naltrexone).