Messiha F S
Texas Tech University Health Sciences Center, School of Medicine, Lubbock.
Neurosci Biobehav Rev. 1988 Fall-Winter;12(3-4):215-8. doi: 10.1016/s0149-7634(88)80045-9.
The effect of acute treatment of two major Tourette's drugs, haloperidol and pimozide given 60 mg/kg, IP over 48 hr, on hepatic alcohol dehydrogenase (L-ADH) and aldehyde dehydrogenase was studied in the female mouse. The effect of these drugs on heart cytoplasmic lactate dehydrogenase (H-LDH) isoenzyme LDH1 (M) and LDH2 (H) was also measured. Both haloperidol and pimozide significantly inhibited cytoplasmic L-ADH and L-ALDH from controls. Conversely, the haloperidol treatment was associated with induction of both H-LDH isoenzymes studied. Injection of pimozide, 25 mg/kg, IP, to rats with preference to ethanol drinking, caused aversion to voluntary intake of 5% ethanol consumption. This suggests that pimozide produced inhibition of L-ADH in another species and thereby causing aversion to ethanol drinking or may be related to dopaminergic antagonist property. This inhibition of these drugs on the oxidative and reductive pathways of biogenic amine aldehydes may be implicated in and/or associated with the underlying mechanism(s) of action.
研究了两种主要用于治疗妥瑞氏症的药物,即氟哌啶醇和匹莫齐特(以60毫克/千克的剂量腹腔注射,持续48小时)对雌性小鼠肝脏乙醇脱氢酶(L-ADH)和乙醛脱氢酶的急性治疗效果。还测定了这些药物对心脏细胞质乳酸脱氢酶(H-LDH)同工酶LDH1(M)和LDH2(H)的影响。氟哌啶醇和匹莫齐特均显著抑制了对照组的细胞质L-ADH和L-ALDH。相反,氟哌啶醇治疗与所研究的两种H-LDH同工酶的诱导有关。给偏爱饮用乙醇的大鼠腹腔注射25毫克/千克的匹莫齐特,导致其厌恶自愿摄入5%的乙醇。这表明匹莫齐特在另一种物种中抑制了L-ADH,从而导致对乙醇饮用的厌恶,或者可能与多巴胺能拮抗剂特性有关。这些药物对生物胺醛的氧化和还原途径的抑制作用可能与潜在的作用机制有关。