Thebaine induces anaphylactic reactions via the MRGPRX2 receptor pathway on mast cells.

Morphine derivatives are clinically important anesthetic and sedative drugs, which often show anaphylactic side effects. Mas-related G-protein coupled receptor member X2 (MRGPRX2) triggers mast cell degranulation, which is important process in anaphylactic reactions. MRGPRX2-HEK293 and LAD2 cell membrane chromatographic (CMC) models were used to screen morphine derivatives binding to MRGPRX2. Furthermore, most morphine derivatives significantly enhanced Ca2+ mobilization. More importantly, thebaine was found to effectively promote histamine release. Thebaine induced the increased release of ß-hexosaminidase and high secretion level of cytokines, confirming that thebaine could further trigger anaphylactic reactions and promote subsequent inflammatory reactions. Moreover, the ability of thebaine inducing degranulation and the release of allergenic mediators in mast cells was significantly decreased after MRGPRX2 knockdown, which proved that MRGPRX2 is the key media for thebaine-induced anaphylactic reactions. Significant hind paw swelling and hypothermia in mice after injecting thebaine suggested that thebaine could trigger anaphylactic reactions in vivo.

What do we know about health risks related to thebaine in food?

Opium alkaloids such as morphine and thebaine occur in the latex of Papaver somniferum varieties. Some varieties are used for both, pharmaceutical opium alkaloid generation and poppy seed production for food use. Poppy seeds can be contaminated with opium alkaloid-containing latex, e.g. during harvesting. In recent years, poppy seed contamination with opium alkaloids, including thebaine, gave repeatedly reasons for concern in Europe. So far, risk assessments regarding opium alkaloids in poppy seeds were mainly based on the morphine level, whereas other opium alkaloids thereunder thebaine could not be finally evaluated due to lack of data. However, available limited data indicate that thebaine exhibits a higher acute toxic potential than morphine. Therefore, exposure to thebaine by consumption of poppy seed-containing food could pose a health risk. Here, we discuss the recent knowledge regarding thebaine's toxicological profile available for the assessment of potential health risks associated with its consumption via food.

Buprenorphine hydrochloride: determination of analgesic potency.

An open evaluation of relief from severe pain following major abdominal operations was carried out on at least ten patients, who had given written consent, with 0.1 to 0.4 mg doses of buprenorphine hydrochloride administered intramuscularly. Statistical analysis of the data showed that 0.3 mg of this compound provided quite satisfactory relief from pain for up to six hours. Seven more consenting patients were given buprenorphine hydrochloride 0.5 to 0.6 mg, but they did not receive much greater or longer pain relief than those receiving 0.3 to 0.4 mg. However, the latter patients were younger and heavier. It was concluded that buprenorphine hydrochloride 0.2 to 0.4 mg provided relief of severe pain probably as well as is observed with morphine 10 mg for the average-size patient, but the duration of pain relief with the new compound is substantially longer than with other strong analgesics previously tested. The only common side effect noted was drowsiness, which was observed during the analgesic action of the compound. No appreciable alterations were seen in the respiration, pulse rate and blood pressure. On the basis of these tests, buprenorphine hydrochloride appears to be a satisfactory analgesic for severe postoperative pain, and it deserves extensive study.