Diacetylmorphine (heroin), discovered in 1894, is produced from morphine by simple chemical acetylation. Heroin, though metabolized to morphine in the body, is more lipophilic than morphine and crosses the blood brain barrier (BBB) more readily, giving a greater rush with IV injection and a relatively shorter time of action (2 hr). It has no real medical benefit over morphine, so its synthesis and sale is banned in most countries.
Codeine (3-methylmorphine) is synthesized from morphine and is better absorbed by mouth, though it has only about 20% of the analgesic potency. It is primarily used for headache or backache and is unlikely to give euphoria or produce addiction. It is commonly used in cough suppressants and can lead to constipation as a side effect. Codeine is avoided in patients taking MAO inhibitors.
Etorphine, discovered in the 1960s, is a morphine-like analog that is 1000x more potent; it is used primarily in the veterinary field to immobilize wild animals; for example one dart can hold enough etorphine to halt an elephant or rhino.
Pentazocine is a mixed agonist and antagonist, where low doses act similarly to morphine but increasing doses do not. Therefore, higher doses do not depress respiration dangerously, but hallucinations and dysphoria (rather than euphoria) increase, presumably due to interaction at KOR. Pentazocine can also lead to dependence.
Propoxyphene was withdrawn by the FDA in November 2010 because new clinical data showed it increased the risk of serious or fatal heart rhythm irregularities and that the medical benefits did not outweigh the risks. Taken at efficacious doses, propoxyphene could result in problems in the heart’s electrical activity, leading to sudden death. Propoxyphene was a prescription drug sold alone (Darvon) or in combination with acetaminophen (Darvocet) and had been approved for mild to moderate pain relief since 1957 (FDA, 2010).