2-METHYL-AP-237 is an opioid analgesic drug that was widely used in China to treat pain in cancer patients as of 1986.It is one of the most potent compound among a series of analgesic acyl piperazines compounds first synthesized and reported in Japan in the 1970s.:
2-METHYL-AP-237 has analgesic potency comparable to that of morphine but with a relatively higher therapeutic index.:
The drug were initially claimed to be a non-narcotic analgesic. However, subsequent studies have shown 2-METHYL-AP-237 and similar acyl piperazines to be potent and selective agonists of μ-opioid receptor (MOR) with relatively low affinity for the δ-opioid receptor and the κ-opioid receptor. In accordance with these studies, results from the intravenous self-administration experiments in rats showed that 2-METHYL-AP-237 has a marked reinforcing effect with tolerance and dependence quickly developing. In addition, the morphine antagonist naloxone the effect of AP-237 and precipitates withdrawal symptoms in 2-METHYL-AP-237 treated rats further indicating a mechanism of analgesia mediated via selective agonist activity at μ-opioid receptors.:
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