Racagni G, Cheney D L, Trabucchi M, Costa E
J Pharmacol Exp Ther. 1976 Feb;196(2):323-32.
We have measured acetylcholine (ACh) content and turnover rate (TRACh) in striatum and cortex of rats receiving haloperidol and clozapine i.p. Both clozapine (30 mumol/kg) and haloperidol (10 mumol/kg) reverse the decrease in striatal TRACh elicited by apomorphine (11 mumol/kg) while each antipsychotic affects the steady state and the TRACh in striatum differently. Haloperidol fails to change striatal ACh content but increases the TRACh; chozapine (15 and 30 mumol/kg) neither decreases the content of ACh nor changes the TRACh in striatum. Moreover, 60 or 90 mumol/kg of clozapine causes a 40% decrease in ACh content without affecting the TRACh. Clozapine, but not haloperidol, antagonizes the increase in ACh content and the decrease in TRACh elicited by arecoline (64 mumol/kg) and oxotremorine (9 mumol/kg) in striatum. Clozapine resembles trihexylphenidyl (14 mumol/kg) and benztropine (12 mumol/kg) because it decreases the ACh content of striatum without changing the TRACh. Moreover, clozapine and benztropine reverse the increase in striatal TRACh elicited by haloperidol. The increase in striatal TRACh elicited by haloperidol could be of value to explain the extrapyramidal action of this drug. The anticholinergic action of clozapine could explain the absence of extrapyramidal side effects observed with this drug.
我们已测量了腹腔注射氟哌啶醇和氯氮平的大鼠纹状体和皮层中的乙酰胆碱（ACh）含量及周转率（TRACh）。氯氮平（30 μmol/kg）和氟哌啶醇（10 μmol/kg）均可逆转阿扑吗啡（11 μmol/kg）引起的纹状体TRACh降低，然而每种抗精神病药物对纹状体的稳态和TRACh的影响不同。氟哌啶醇未能改变纹状体ACh含量，但增加了TRACh；氯氮平（15和30 μmol/kg）既未降低ACh含量，也未改变纹状体的TRACh。此外，60或90 μmol/kg的氯氮平可使ACh含量降低40%，而不影响TRACh。氯氮平而非氟哌啶醇可拮抗槟榔碱（64 μmol/kg）和氧化震颤素（9 μmol/kg）引起的纹状体ACh含量增加及TRACh降低。氯氮平类似于苯海索（14 μmol/kg）和苄托品（12 μmol/kg），因为它可降低纹状体ACh含量而不改变TRACh。此外，氯氮平和苄托品可逆转氟哌啶醇引起的纹状体TRACh增加。氟哌啶醇引起的纹状体TRACh增加可能有助于解释该药物的锥体外系作用。氯氮平的抗胆碱能作用可能解释了该药物未观察到锥体外系副作用的原因。
