부산대학교 도서관

Background/Objectives: 1,4-BD is abused at dance raves and nightclubs, where ethanol (ETOH) and other drug use is prevalent. We examined interactions between 1,4-BD and ETOH as well as the 'club drugs,' flunitrazepam and ketamine. Methods: Drug doses were derived from our lab (1,4-BD, ETOH) or literature review (flunitrazepam, ketamine) and administered by i.p. route. Male CD-1 mice received 1,4-BD 600mg/kg alone (n = 10), ETOH 2g/kg + 1,4-BD 600mg/kg (n = 10), ETOH 2g/kg + 1,4-BD 1g/kg (n = 10), ketamine 100mg/kg + 1,4-BD 600mg/kg (n = 10), or flunitrazepam 5mg/kg + 1,4-BD 600mg/kg (n = 10). Toxicity was evaluated every 10 min. by the righting reflex and rotarod test. Results: Mice receiving 1,4-BD (600mg/kg) alone, and in combination with flunitrazepam, ketamine, and ETOH, lost their righting reflex for 110, 180, 110, and 0 min., respectively. Mice receiving high dose 1,4-BD (1g/kg) and ETOH lost their righting reflex for 300 min. Mice receiving 1,4-BD (600mg/kg) alone, and in combination with flunitrazepam and ketamine, failed the rotarod test for 210, 240, and 190 min., respectively. Mice receiving 1,4-BD (600mg/kg) and ETOH failed the rotarod test for the initial 50 min., followed by a 50-min. period when mice recovered their ability to perform the rotarod test. However, toxicity then recrudesced with all mice again failing the rotarod test for 120 min. Mice receiving high-dose 1,4-BD (1g/kg) and ETOH failed the rotarod test for a sustained 500 min. Conclusions: For the righting reflex, rank order of toxicity was: 1,4-BD (1g/kg) + ETOH [is greater than] 1,4-BD + flunitrazepam [is greater than] 1,4-BD alone and 1,4-BD + ketamine [is greater than] 1,4-BD (600mg/kg) + ETOH. For the rotarod test, it was: 1,4-BD (1g/kg) + ETOH [is greater than] 1,4-BD + flunitrazepam [is greater than] 1,4-BD alone [is greater than] 1,4-BD + ketamine. 1,4-BD (600mg/ kg) and ETOH recrudescing toxicity may represent dose-dependent, delayed 1,4-BD toxicity from greater alcohol dehydrogenase affinity for ETOH.
Quang L(1), Desai M(2), Boyer E(1), Shannon M(1), Woolf A(1), Maher T(2). (1) Children's Hospital, Massachusetts/Rhode Island Poison Control Center, Harvard Medical School, (2) Massachusetts College of Pharmacy and Health [...]