Osadebe P O
Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka.
Boll Chim Farm. 2004 Apr;143(3):116-9.
Four previously stynthesized derivatives of 3- (4-benzyl-1-piperazinyl)-1-phenylpropanol were screened for analgesic activity in albino mice using a variation of the Eddy and Lambach hot plate method. The result showed that the most significant analgesic effect was elicited by the parent secondary 3-piperazinylpropanol, namely 3-(4-benzyl-1-piperazinyl)-1-phenylpropanol. Its esterification products with propanoyl, benzoyl and phenylacetyl chlorides exhibited reduced analgesic properties. The percent maximum protection against thermal pain produced by Aspirin (71.43%) was twice as high as that produced by the most active of the four derivatives (43.65%). The analgesic effect of the compounds was dose dependent. From acute toxicity studies in mice, the LD50 values were estimated to be in range of moderate toxicity (89.74 to 243 mg/kg). The most active of the compounds studied, namely, 3-(4-benzyl-1-piperazinyl-1-phenylpropanols, was also found to be the most toxic. The margin between its safe doses and its LD50 (89.74 mg/kg) was found to be very narrow. Esterification of the 3-(4-benzyl-1-piperazinyl)-1-phenylpropanol led to decrease in its analgesic activity and also a decrease in its toxicity.
采用Eddy和Lambach热板法的一种变体，对白化病小鼠中四种先前合成的3-(4-苄基-1-哌嗪基)-1-苯基丙醇衍生物进行了镇痛活性筛选。结果表明，母体仲3-哌嗪基丙醇，即3-(4-苄基-1-哌嗪基)-1-苯基丙醇，产生了最显著的镇痛效果。其与丙酰氯、苯甲酰氯和苯乙酰氯的酯化产物镇痛性能降低。阿司匹林产生的对热痛的最大保护百分比(71.43%)是四种衍生物中活性最高的(43.65%)的两倍。这些化合物的镇痛作用呈剂量依赖性。从小鼠的急性毒性研究中，估计半数致死量(LD50)值处于中等毒性范围(89.74至243毫克/千克)。所研究的化合物中活性最高的，即3-(4-苄基-1-哌嗪基)-1-苯基丙醇，也被发现毒性最大。发现其安全剂量与半数致死量(89.74毫克/千克)之间的差距非常小。3-(4-苄基-1-哌嗪基)-1-苯基丙醇的酯化导致其镇痛活性降低，毒性也降低。
