THREE TYPES OF OPIOID DRUG–RECEPTOR INTERACTIONS

Three types of opioids are classified by the effect that they have on the mu receptors on cells. They are the full agonist, the partial agonist and the antagonist.

As used here, an agonist is something that stimulates or produces an effect.  Agonist is derived from the Late Latin agnista which means contender which is derived from the Greek agonists which also means contestant which came from agon which means contest. An agonist is a chemical contestant or contender.

An antagonist is something that blocks an effect.  Antagonist is derived from antagonize which is derived from the Greek antagonizesthal which means to struggle against which is derived from agonizesthal which means to struggle which is derived from agon which means contest.

FULL AGONISTS

Full agonists are opioid drugs that bind to mu opioid receptors in the brain, and cause them to produce endorphins which give analgesic (pain relief) and, depending on the dose and frequency, addictive effects and feelings of euphoria.  Unless an individual’s metabolism and DNA prevent it, the larger the dose of a full agonist, the more mu receptors are activated and the larger the effects.  Examples of full agonists are oxycodone, methadone, codeine, heroin and morphine.

PARTIAL AGONISTS

Partial agonists are drugs that bind primarily to mu opioid receptors and cause them to produce endorphins but to a much lesser extent than full agonists. Buprenorphine®, Suboxone® and Subutex® are partial agonists.

When the dosage of a full agonist is increased, the opioids will activate more receptors and create more endorphins.  When the dosage of a partial agonist is increased, there is only a small increase, if any, in the production of endorphins.

COMPARING EFFECTS OF FULL AGONIST AND PARTIAL AGONIST

One way of viewing this is to liken the effects of an opioid to the operation of an elevator in a ten story building that requires a specific code that must be entered for someone to use the elevator to reach a specific floor.

Each time a person takes a full agonist it contains a code, unless significantly modified by the DNA and the way the full agonist is metabolized, which will allow the elevator to reach a certain floor.  In low doses, the elevator code (number of endorphins created) may only allow the elevator to reach the second floor.  However, as the full agonist dosage increases, the elevator code can now rise to higher floors and eventually to the tenth floor.

A partial agonist, like buprenorphine, will only stimulate the mu receptors to produce a certain amount of endorphins.   Using our elevator example, when an individual takes a partial agonist in small doses it may contain a code that allows the elevator to rise to the second floor.  However, no matter how much the dosage of the partial agonist increases, the code in the partial agonist will not allow the elevator to rise above the fourth floor.

This is why it is much harder to abuse a partial agonist than a full agonist.  The partial agonist has a lower intrinsic activity than full agonists but some, like buprenorphine, have a much higher affinity than full agonists and its disassociation time is much longer than most opiates and opioids (except for methadone).

HOW PARTIAL AGONISTS CAN TRIGGER WITHDRAWAL

Apparently mu receptors have more affinity for partial agonists like buprenorphine than  they have for full agonists.  For example, if someone has been taking a full agonist like OxyContin ® and there is still some active OxyContin ® in their body, taking a partial agonist like buprenorphine causes the mu receptors to accept the partial agonist and this prevents the full agonists from reaching the mu receptors.  If the full agonist was still stimulating some of the receptors before the introduction of the partial agonist and causing our elevator to rise to the eighth floor, then by blocking the access to the mu receptors, the buprenorphine only allows the elevator to rise to the fourth floor and this can cause immediate withdrawal symptoms.

This effect is increased because buprenorphine is slower acting than many other opioids and remains in the mu receptor blocking it for a longer period of time.  Because the ultimate desire of someone who is detoxing from an opiate is the replacement of the endorphin production by the body, full agonist opioids actually work to prevent this by sending a signal to the body that there is no need to produce natural endorphins.  A partial agonist will often cause a signal to be sent to the body that the natural endorphin production needs to be increased.

ANTAGONISTS

Antagonists are drugs that bind to the mu opioid receptors but don’t stimulate the production of endorphins.  What they do is prevent other opioids from stimulating the mu receptors. This is why someone who is taking oxycodone (the generic name for OxyContin ®)  to stimulate endorphin production can go into withdrawal if they take an antagonist.  The antagonist blocks the mu receptors and does not allow the oxycodone to bind to the mu receptor so there is no production of endorphins.  Naloxone ® and naltrexone are opioid antagonists. (Studies have shown that buprenorphine can be an antagonist at kappa receptors but this antagonist effect does not appear to be a significant factor in using buprenorphine to withdraw people from other opioids or opiates.)