Matsuyama K, Yamashita C, Sendoh T, Noda A, Goto S, Iguchi S
J Pharmacobiodyn. 1983 Dec;6(12):932-7. doi: 10.1248/bpb1978.6.932.
Perry's hypothesis that hydrazine (Hz) derived from isoniazid (INH) treatment plays an important role in the elevation of brain gamma-aminobutyric acid (GABA) levels was reexamined by measuring Hz and GABA levels in the brain after the treatment with 50 mg/kg of INH or different doses of Hz. The treatment with 50 mg/kg of INH to rats resulted in the elevation of GABA levels in rat whole brain. The maximum levels of GABA increased about twice at 4 h from 2.06 +/- 0.4 mumol/g wet wt. in the control group to 3.61 +/- 0.4 mumol/g wet wt. in INH treated group. In this case, brain levels of Hz ranged from 25.6 to 80.8 ng/g wet wt. within 10 h. On the other hand, Hz levels after the treatment with 0.5 mg/kg of Hz were about five times higher than those after INH treatment. However, 0.5 mg/kg of Hz treatment did not increase brain GABA levels at all. Perry's hypothesis was denied by the fact that brain Hz levels after INH treatment were too low to elevate brain GABA levels.
通过测量用50mg/kg异烟肼(INH)或不同剂量的肼(Hz)处理后大脑中的Hz和γ-氨基丁酸(GABA)水平,重新检验了佩里的假说,即异烟肼治疗产生的肼在提高大脑GABA水平中起重要作用。给大鼠注射50mg/kg的INH导致大鼠全脑GABA水平升高。GABA的最高水平在4小时时从对照组的2.06±0.4μmol/g湿重增加了约两倍,达到INH处理组的3.61±0.4μmol/g湿重。在这种情况下,大脑中的Hz水平在10小时内为25.6至80.8ng/g湿重。另一方面,用0.5mg/kg的Hz处理后的Hz水平比INH处理后的水平高约五倍。然而,0.5mg/kg的Hz处理根本没有提高大脑GABA水平。INH处理后大脑中的Hz水平过低,无法提高大脑GABA水平,这一事实否定了佩里的假说。