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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Properties of some 1-arylpiperazines as antagonists of stereotyped behaviors mediated by central serotonergic receptors in rodents.

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)[1]


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