Bucinnazine (AP-237, 1-butyryl-4-cinnamylpiperazine) is an
opioid analgesic drug that was widely used in China to treat
pain in
cancer patients as of 1986.[1] It is one of the most potent compounds among a series of piperazine-
amides first synthesized and reported in Japan in the 1970s.[2][3][4] Bucinnazine has analgesic potency comparable to that of
morphine but with a relatively higher
therapeutic index.
The drug was initially claimed to be a non-narcotic analgesic. However, subsequent studies have shown bucinnazine 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.[5] In accordance with these studies, results from the intravenous self-administration experiments in rats showed that bucinnazine has a marked reinforcing effect with
tolerance and
dependence quickly developing.[1] In addition, the morphine antagonist naloxone reverses the effect of bucinnazine and precipitates
withdrawal symptoms in bucinnazine treated rats further indicating a mechanism of analgesia mediated via selective agonist activity at μ-opioid receptors.
Derivatives
2-methyl-AP-237 has been sold on the grey market as a
designer opioid, first identified by a police forensic laboratory in Slovenia in March 2019.[6][7][8] In 2023, the
United States Department of Justice took criminal action against two individuals for selling 2-methyl-AP-237 under the false pretenses that such product was intended for
'research purposes' only. One of the pair was sentenced to five years in
federal prison.[9]
^Nishimura N, Kiuchi M, Kanetake Y, Takahashi T (June 1970). "[Clinical exaluation of a new analgesic agent Ap-237]". Masui. The Japanese Journal of Anesthesiology. 19 (6): 653–656.
PMID4916908.
^Carrano RA, Kimura KK, McCurdy DH (January 1975). "Analgesic and tolerance studies with AP-237, a new analgesic". Archives Internationales de Pharmacodynamie et de Therapie. 213 (1): 41–57.
PMID1156018.
^Carrano RA, Kimura KK, Landes RC, McCurdy DH (January 1975). "General pharmacology of a new analgesic-AP-237". Archives Internationales de Pharmacodynamie et de Therapie. 213 (1): 28–40.
PMID1156016.
^Barlocco D, Cignarella G, Greco G, Novellino E (October 1993). "Computer-aided structure-affinity relationships in a set of piperazine and 3,8-diazabicyclo[3.2.1]octane derivatives binding to the mu-opioid receptor". Journal of Computer-Aided Molecular Design. 7 (5): 557–571.
Bibcode:
1993JCAMD...7..557B.
doi:
10.1007/bf00124362.
PMID8294946.
S2CID23360530.