How could a drug be both agonist and antagonist?
Imagine a narcotic agonist that fits perfectly onto an endorphin receptor (like morphine).
Imagine a narcotic antagonist that doesn’t fit perfectly, so it latches onto the endorphin receptor and blocks it (like naloxone).
What if you had a drug that looked like both the agonist and antagonist and it depended which side of the chemical got on the receptor? That’s what a narcotic agonist/antagonist is like. This would not be a powerful analgesic narcotic because only 50% of the drug would be stimulating the receptors.
The advantage of having this drug
Individuals normally abuse narcotics because they want that euphoric effect. When they take a narcotic, all their receptors are going to be stimulated. To be addicted, 100% have to be stimulated all the time. If you use this type of drug, only 50% are stimulated, so the effects are milder and the chance of abuse is less.
- Pentazocine (Talwin) – inj., p.o. – Schedule IV
- Butorphanol (Stadol) – inj – not scheduled
- Nalbuphine (Nubain) – inj. – not scheduled
So we have less abuse and addiction potential but lo and behold, the first one, pentazocine, is a schedule IV controlled substance. This turned out to be a terribly abused one and it took years for the FDA to figure it out. Somebody figured out that if they could take Pentazocine and another antihistamine that isn’t on the market anymore, crush it, solubilize it, and shoot it in their veins, they’d have the greatest high in the world. So they’d say, “I have this terrible knee pain but I don’t want a strong narcotic, I want pentazocine and also my allergies are acting up.” So they’d get a prescription for pentazocine and the antihistamine. By the time people figured it out, the FDA said we’re pulling this from the market because there’s more bad than good associated with this drug.
The manufacturer wanted time to fix this. They changed the name from Talwin to Talwin Nx and added another ingredient to the drug. What could Nx be? They added naloxone to this drug. Since it was a new combination it had to get approved again. It was on a fast-track plan so it only took a matter of months for approval. What did we say about oral absorption about naloxone? It’s not effective, that’s why it’s only found as an injectable. If you took this Talwin Nx tablet orally, you would take in the pentazocine and the naloxone wouldn’t do anything. If you crushed this tablet up and shot it in your veins, the naloxone would block the receptors and the pentazocine wouldn’t be able to work. So if you took it orally, it would work as intended. If you took it as the injectable form, it wouldn’t work at all. The manufacturer saved the drug from being completely pulled.
Remember when we mentioned two situations where you wouldn’t want to use the most potent narcotics because they would have the opposite effect? Gall stones (Biliary pressure) and Labor (uterus relaxation). For these issues we would go with a narcotic agonist/antagonist.
Would this be good for an addict? They would go into withdrawal, not as severe, but they would go into withdrawal. It’s not a good treatment for addiction.
