Owen J A, Elliott J, Jhamandas K, Nakatsu K
Can J Physiol Pharmacol. 1984 Apr;62(4):446-51. doi: 10.1139/y84-071.
3,6-Dipropanoylmorphine (DPM), 3,6-dibutanoylmorphine (DBM), and 3,6-dihexanoylmorphine (DHM) were prepared as prospective long-acting narcotic analgesics. The purity and structure of these compounds were authenticated by high pressure liquid chromatography and direct probe mass spectrometry. In aqueous solution the stability of the HCI salts of these compounds decreased with increasing alkyl chain length such that DHM underwent rapid hydrolysis to 6-monohexanoylmorphine (MHM). A comparison of DPM, DBM, and MHM with morphine (MO) and 3,6-diacetylmorphine (DAM, heroin) in the electrically stimulated guinea pig ileum myenteric plexus longitudinal muscle strip preparation (GUPIL) revealed similar potencies and efficacies for all compounds, but marked differences in the onset of drug action (MO greater than DAM greater than MHM greater than DPM greater than DBM, faster to slower). In a periodically washed GUPIL preparation DBM and MHM were five times longer acting than MO, DAM or DPM.
3,6-二丙酰吗啡（DPM）、3,6-二丁酰吗啡（DBM）和3,6-二己酰吗啡（DHM）被制备为潜在的长效麻醉性镇痛药。这些化合物的纯度和结构通过高压液相色谱法和直接探针质谱法进行了鉴定。在水溶液中，这些化合物盐酸盐的稳定性随着烷基链长度的增加而降低，以至于DHM迅速水解为6-单己酰吗啡（MHM）。在电刺激豚鼠回肠肌间神经丛纵肌条制备（GUPIL）中，将DPM、DBM和MHM与吗啡（MO）和3,6-二乙酰吗啡（DAM，海洛因）进行比较，结果显示所有化合物的效价和效能相似，但药物作用的起效时间存在显著差异（MO大于DAM大于MHM大于DPM大于DBM，从快到慢）。在定期冲洗的GUPIL制剂中，DBM和MHM的作用时间比MO、DAM或DPM长五倍。
