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

KJ Simansky and LE Schechter

Department of Pharmacology, Medical College of Pennsylvania at Eastern Pennsylvania Psychiatric Institute, Philadelphia.

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)

Volume 247, Issue 3, pp. 1073-1081, 12/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics

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