Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
Chem Biol Interact. 2010 Sep 6;187(1-3):421-4. doi: 10.1016/j.cbi.2010.02.036. Epub 2010 Feb 26.
Cocaine access to brain tissue and associated cocaine-induced behaviors are substantially reduced in rats and mice by significant plasma levels of an enzyme that rapidly metabolizes the drug. Similar results have been obtained in rodents and humans with therapeutic anti-cocaine antibodies, which sequester the drug and prevent its entry into the brain. We show that an efficient cocaine hydrolase can lead to rapid unloading of anti-cocaine antibodies saturated with cocaine, and we provide a theoretical basis for the hypothesis that dual therapy with antibody and hydrolase enzyme may be especially effective.
在大鼠和小鼠中,通过显著提高可快速代谢药物的酶的血浆水平,可卡因进入脑组织和相关可卡因诱导的行为受到极大抑制。在具有治疗性抗可卡因抗体的啮齿动物和人类中也获得了类似的结果,抗可卡因抗体可隔离药物并防止其进入大脑。我们表明,高效可卡因水解酶可导致与可卡因饱和的抗可卡因抗体快速卸载,这为双抗体和水解酶酶治疗的假说提供了理论依据,该假说可能特别有效。