Derlet R W, Tseng J C, Albertson T E
Division of Emergency Medicine, University of California, Davis, School of Medicine.
Am J Emerg Med. 1992 May;10(3):211-6. doi: 10.1016/0735-6757(92)90211-F.
The effect of caffeine when combined with cocaine or amphetamine was studied in rats. Animals were pretreated with intraperitoneal vehicle (normal saline [NS]) or caffeine 100 mg/kg, then challenged with intraperitoneal cocaine (0, 35, 50, 70, or 90 mg/kg) or intraperitoneal d-amphetamine (0, 15, 25, 35, or 42 mg/kg). Animal behavior, time to, and incidences of seizures and death were recorded. This dose of caffeine alone did not cause seizures or death. Caffeine pretreatment significantly increased the incidence of overt seizures induced by either cocaine or amphetamine. Caffeine increased the incidence of cocaine-induced death from 10% to 90% at the 70 mg/kg cocaine dose (P less than .01). Caffeine increased amphetamine-induced death from 0% to 80% at 15 mg/kg (P less than or equal to .01), 10% to 70% at 25 mg/kg (P less than or equal to .01), and 30% to 80% at 35 mg/kg (P less than or equal to .01). To investigate mechanisms, additional animals were pretreated with the adenosine agonist, 2-chloroadenosine (2.5 and 10 mg/kg), before being challenged with NS, 90 mg/kg cocaine, or 42 mg/kg amphetamine. Pretreatment with 2-chloroadenosine had no affect in reducing cocaine or amphetamine toxicity. Combination pretreatment with caffeine and 2-chloroadenosine potentiated cocaine toxicity. The phosphodiesterase inhibitor, pentoxifylline, did not potentiate cocaine toxicity. The authors conclude that caffeine potentiates the acute toxicity of both cocaine and amphetamine, and that the failure of 2-chloroadenosine to alter this suggests that the toxicity of the stimulants cocaine and amphetamine may be modulated by nonspecific rather than specific adenosine- or phosphodiesterase-induced mechanisms.
在大鼠中研究了咖啡因与可卡因或苯丙胺合用时的作用。动物腹腔注射溶媒（生理盐水[NS]）或100mg/kg咖啡因进行预处理，然后腹腔注射可卡因（0、35、50、70或90mg/kg）或d-苯丙胺（0、15、25、35或42mg/kg）进行激发。记录动物行为、癫痫发作时间以及癫痫发作和死亡的发生率。单独使用该剂量的咖啡因不会引起癫痫发作或死亡。咖啡因预处理显著增加了可卡因或苯丙胺诱发的明显癫痫发作的发生率。在70mg/kg可卡因剂量时，咖啡因将可卡因诱发的死亡率从10%提高到90%（P<0.01）。咖啡因在15mg/kg时将苯丙胺诱发的死亡率从0%提高到80%（P≤0.01），在25mg/kg时从10%提高到70%（P≤0.01），在35mg/kg时从30%提高到80%（P≤0.01）。为了研究作用机制，在腹腔注射NS、90mg/kg可卡因或42mg/kg苯丙胺进行激发之前，用腺苷激动剂2-氯腺苷（2.5和10mg/kg）对另外的动物进行预处理。用2-氯腺苷预处理对降低可卡因或苯丙胺毒性没有影响。咖啡因和2-氯腺苷联合预处理增强了可卡因毒性。磷酸二酯酶抑制剂己酮可可碱没有增强可卡因毒性。作者得出结论，咖啡因增强了可卡因和苯丙胺的急性毒性，并且2-氯腺苷未能改变这种情况表明，可卡因和苯丙胺等兴奋剂的毒性可能是由非特异性而非特异性腺苷或磷酸二酯酶诱导的机制调节的。
