Jaiswal R K, Gupta K P, Kumar A, Bhargava K P, Ali B
Pharmacology. 1979;19(3):132-7. doi: 10.1159/000137300.
The present study reports the synthesis and characterization of eight new substituted benzylideneamino guanidines. All compounds inhibited the monoamine oxidase (MAO) activity of rat brain mitochondria in vitro. The I50 values were determined and were found to be in the range of 10(-4) to 10(-5) mol/l. Preincubation, dialysis and kinetic studies carried out with isolated brain mitochondria by conventional Dixon plot revealed reversible and noncompetitive type of MAO inhibition. These compounds were also screened for anticonvulsant and antidepressant activities. In the present series of compounds only one compound -- 1-amino-3-(4-chloromethylbenzylidene-amino)guanidine hydroiodide -- was found to afford 20% protection against pentetrazol-induced seizures in mice. 1-Amino-3-(3,4-dichlorobenzylideneamino)guanidine hydroiodide which produced maximum inhibition of MAO activity, also produced reversal of reserpine-induced sedation and miosis into excitation and mydriasis in mice.
本研究报道了8种新的取代亚苄基氨基胍的合成与表征。所有化合物在体外均抑制大鼠脑线粒体的单胺氧化酶（MAO）活性。测定了半数抑制浓度（I50）值，发现其范围为10⁻⁴至10⁻⁵mol/L。通过传统的狄克逊图对分离的脑线粒体进行预孵育、透析和动力学研究，结果显示MAO抑制为可逆的非竞争性类型。还对这些化合物进行了抗惊厥和抗抑郁活性筛选。在本系列化合物中，仅一种化合物——1-氨基-3-（4-氯甲基亚苄基氨基）胍氢碘酸盐——在小鼠中对戊四氮诱导的惊厥提供了20%的保护作用。产生最大MAO活性抑制作用的1-氨基-3-（3,4-二氯亚苄基氨基）胍氢碘酸盐，还使小鼠中利血平诱导的镇静和瞳孔缩小转变为兴奋和瞳孔散大。
