Bucinnazine (AP-237, 1-butyryl-4-cinnamylpiperazine) is an
opioid
Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...
analgesic drug that was widely used in China to treat
pain
Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...
in
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
patients as of 1986.
It is one of the most potent compounds among a series of piperazine-
amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...
s first synthesized and reported in Japan in the 1970s. Bucinnazine has analgesic potency comparable to that of
morphine
Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...
but with a relatively higher
therapeutic index
The therapeutic index (TI; also referred to as therapeutic ratio) is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes ...
.
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
An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an ...
of
μ-opioid receptor
The μ-opioid receptors (MOR) are a class of opioid receptors with a high affinity for enkephalins and beta-endorphin, but a low affinity for dynorphins. They are also referred to as μ(''mu'')-opioid peptide (MOP) receptors. The prototypical Π...
(MOR) with relatively low affinity for the
δ-opioid receptor
The δ-opioid receptor, also known as delta opioid receptor or simply delta receptor, abbreviated DOR or DOP, is an inhibitory 7-transmembrane G-protein coupled receptor coupled to the G protein Gi/G0 and has enkephalins as its endogenous lig ...
and the
κ-opioid receptor
The κ-opioid receptor or kappa opioid receptor, abbreviated KOR or KOP, is a G protein-coupled receptor that in humans is encoded by the ''OPRK1'' gene. The KOR is coupled to the G protein Gi/G0 and is one of four related receptors that bind op ...
. 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.
[ In addition, the morphine antagonist naloxone reverses the effect of bucinnazine and precipitates ]withdrawal symptoms
Drug withdrawal, drug withdrawal syndrome, or substance withdrawal syndrome, is the group of symptoms that occur upon the abrupt discontinuation or decrease in the intake of pharmaceutical or recreational drugs.
In order for the symptoms of wit ...
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.
See also
* AP-238
AP-238 is an opioid designer drug related to drugs such as azaprocin and bucinnazine, with around the same potency as morphine. It was first discovered in Italy in the 1960s but was never marketed, subsequently appearing on the illicit market aro ...
* Azaprocin
Azaprocin is a drug which is an opioid analgesic with approximately ten times the potency of morphine, and a fast onset and short duration of action. It was discovered in 1963, but has never been marketed.
The derivative substituted on the pheny ...
* Diphenpipenol
Diphenpipenol is an opioid analgesic drug invented in the 1970s by Dainippon Pharmaceutical Co. It is chemically a 1-substituted-4-(1,2-diphenylethyl) piperazine derivative related to compounds such as MT-45 and AD-1211, but diphenpipenol is th ...
* MT-45
MT-45 (IC-6) is an opioid analgesic drug invented in the 1970s by Dainippon Pharmaceutical Co. It is chemically a 1-substituted-4-(1,2-diphenylethyl) piperazine derivative, which is structurally unrelated to most other opioid drugs. Racemic MT-4 ...
* Sunifiram
References
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Analgesics
Euphoriants
Mu-opioid receptor agonists
Piperazines
Amides