Owen J A, Nakatsu K
Can J Physiol Pharmacol. 1984 Apr;62(4):452-6. doi: 10.1139/y84-072.
The kinetics of hydrolysis of dipropanoylmorphine (DPM) and dibutanoylmorphine (DBM) in human blood fractions and for diacetylmorphine (DAM) and DBM in rat blood fractions were investigated. In each case the hydrolysis of morphine diesters terminated with the production of the corresponding 6-monoester derivative. Generally, decreases in Km and Vmax were observed for the plasma, red blood cell (RBC) cytosol, and RBC membrane esterases responsible for morphine diester hydrolysis as the alkyl chain length of the ester moiety increased. This resulted in an overall decrease in the rate of hydrolysis of morphine diesters by human or rat blood with longer chain homologs of DAM. The analgesic potency and duration of morphine, DAM, and DBM were assessed at various i.v. dosages in the rat by means of the tail-flick latency test. A comparison of equianalgesic doses of morphine, DAM, and DBM indicated that DAM and DBM were 11.5 and 6 times as potent and 0.8 and 1.2 times as long acting, respectively, as morphine.
研究了二丙酰吗啡（DPM）和二丁酰吗啡（DBM）在人血液组分中的水解动力学，以及二乙酰吗啡（DAM）和DBM在大鼠血液组分中的水解动力学。在每种情况下，吗啡二酯的水解都以相应的6-单酯衍生物的产生而终止。一般来说，随着酯部分烷基链长度的增加，负责吗啡二酯水解的血浆、红细胞（RBC）胞质溶胶和RBC膜酯酶的Km和Vmax均降低。这导致人或大鼠血液对吗啡二酯的水解速率随着DAM的长链同系物而总体下降。通过甩尾潜伏期试验，在大鼠中以不同静脉注射剂量评估了吗啡、DAM和DBM的镇痛效力和持续时间。对吗啡、DAM和DBM等效镇痛剂量的比较表明，DAM和DBM的效力分别是吗啡的11.5倍和6倍，作用时间分别是吗啡的0.8倍和1.2倍。
