Ana Karen Ruiz-Quinonez
A.K. Ruiz-Quiñonez, T. Browne Jr,, Z. Espinosa-Riquer, C. González-Espinosa, S.L. Cruz, Department of Pharmacobiology, Cinvestav, Mexico City, Mexico
Background: With extensive opioid use and misuse, and the presence of adulterants in street drugs, deaths from opioid overdoses have dramatically increased. Among other compounds, heroin can be laced with the anthelmintic drug levamisole (which has been detected in samples from Ecuador and parts of the U.S.); however, few preclinical studies have addressed the consequences of combining levamisole with opioids. The aim of this study was to investigate the lethal, analgesic and hematological effects of morphine combined with levamisole in male Swiss Webster mice.
Methods: Using independent groups of animals (n=10), we conducted the following experiments: a) mice were i.p injected with the lethal dose at 10% (LD10) of morphine (100 mg/kg), levamisole (31.6 mg/kg) or morphine plus levamisole; b) same as in a, but animals received naloxone (10 or 30 mg/kg) 20 min before each treatment; c) mice were treated twice a day for 35 or 41 days with a sublethal levamisole dose to determine if mortality occurred after chronic treatment; d) mice received 17.7 mg/kg levamisole twice daily for two weeks. The third week animals were divided to receive one of the following treatments: levamisole, morphine or morphine plus levamisole. Control animals received only saline. Antinociception was evaluated by the tail tail-flick test after single or repeated morphine administration in mice pre-treated with levamisole injections. In selected groups we conducted automated hematological analysis.
Results: Levamisole: a) significantly potentiated morphine lethality and this effect was partially prevented only with the highest dose of naloxone (30 mg/kg); b) blocked acute morphine’s antinociceptive effects without preventing tolerance development; c) decreased hemoglobin levels and the number of neutrophils, but not that of leucocytes, lymphocytes, monocytes or erythrocytes.
Conclusions: Levamisole increases morphine lethality, decreases naloxone efficacy to counteract morphine effects and causes serious deleterious hematological effects.
Financial Support: This work was supported by the Colombo Plan Drug Advisory Program and the scholarship 718462 (AKRQ).