Simansky K J, Schechter L E
Department of Pharmacology, Medical College of Pennsylvania at Eastern Pennsylvania Psychiatric Institute, Philadelphia.
J Pharmacol Exp Ther. 1988 Dec;247(3):1073-81.
This investigation evaluated the effects of the 1-arylpiperazines (1-(1-naphthyl)piperazine (1-NP), 1-(2-[4-aminophenylethyl]-4-[3-trifluoromethylphenyl]piperazine (PAPP), 1-(3-trifluoromethylphenyl)piperazine (TFMPP) and 1-(3-chlorophenyl)piperazine (mCPP) on head-twitching elicited by central 5-hydroxytryptamine2, (5-HT2) agonists and on the 5-HT motor syndrome associated with stimulating 5-HT1A receptors in rodents. 1-NP (0.25-16.0 mumol/kg i.p.) dose-dependently inhibited head twitching produced by carbidopa (100 mumol/kg i.p.) plus 5-hydroxy-L-tryptophan (1000 mumol/kg i.p.) in mice. Pretreatment with 4 mumol/kg of 1-NP shifted the entire dose-response curve for head-twitching induced by quipazine (0.33-46.7 mumol/kg i.p.) to the right without reducing locomotor stimulation produced by quipazine (8 mumol/kg) in mice placed in novel photocell cages. 1-NP, PAPP, TFMPP and mCPP (8 mumol/kg) antagonized twitching after 5-methoxy-N,N-dimethyltryptamine (100 mumol/kg i.p.) or 5-hydroxy-L-tryptophan. In rats, these arylpiperazines (1-32 mumol/kg) dose-dependently antagonized twitching elicited by quipazine (10 mumol/kg) without producing correlated alterations in locomotion. 1-NP, PAPP, and mCPP were equipotent and 6-fold more potent than TFMPP against twitching. None of these arylpiperazines caused twitching. 1-NP (4 mumol/kg) also antagonized twitching following the direct 5-HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (6 mumol/kg i.p.) but not after the thyrotropin releasing hormone analog MK-771 (20 mumol/kg i.p.) in rats. Larger doses of 1-NP (4-32 mumol/kg) and PAPP (64 mumol/kg) but not TFMPP or mCPP (16-128 mumol/kg), also reduced the incidence of the 5-HT syndrome produced by 5-methoxy-N,N-dimethyltryptamine (30 mumol/kg) in rats.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究评估了1-芳基哌嗪类化合物（1-（1-萘基）哌嗪（1-NP）、1-（2-[4-氨基苯乙基]-4-[3-三氟甲基苯基]哌嗪（PAPP）、1-（3-三氟甲基苯基）哌嗪（TFMPP）和1-（3-氯苯基）哌嗪（mCPP））对中枢5-羟色胺2（5-HT2）激动剂引发的头部抽搐以及对啮齿动物中刺激5-HT1A受体相关的5-HT运动综合征的影响。1-NP（0.25 - 16.0 μmol/kg腹腔注射）剂量依赖性地抑制了卡比多巴（100 μmol/kg腹腔注射）加5-羟-L-色氨酸（1000 μmol/kg腹腔注射）在小鼠中引发的头部抽搐。用4 μmol/kg的1-NP预处理可使喹哌嗪（0.33 - 46.7 μmol/kg腹腔注射）诱导的头部抽搐的整个剂量反应曲线右移，而不降低置于新型光电笼中的小鼠中喹哌嗪（8 μmol/kg）产生的运动刺激。1-NP、PAPP、TFMPP和mCPP（8 μmol/kg）拮抗5-甲氧基-N,N-二甲基色胺（100 μmol/kg腹腔注射）或5-羟-L-色氨酸后的抽搐。在大鼠中，这些芳基哌嗪（1 - 32 μmol/kg）剂量依赖性地拮抗喹哌嗪（10 μmol/kg）引发的抽搐，且不引起运动的相关改变。1-NP、PAPP和mCPP的效力相当，且在拮抗抽搐方面比TFMPP强6倍。这些芳基哌嗪均未引起抽搐。1-NP（4 μmol/kg）还拮抗了直接5-HT2激动剂1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷（6 μmol/kg腹腔注射）后的抽搐，但在大鼠中对促甲状腺激素释放激素类似物MK-771（20 μmol/kg腹腔注射）后的抽搐无拮抗作用。更大剂量的1-NP（4 - 32 μmol/kg）和PAPP（64 μmol/kg），但不是TFMPP或mCPP（16 - 128 μmol/kg），也降低了5-甲氧基-N,N-二甲基色胺（30 μmol/kg）在大鼠中产生的5-HT综合征的发生率。（摘要截短于250字）
