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)
Simansky
K J
KJ
Department of Pharmacology, Medical College of Pennsylvania at Eastern Pennsylvania Psychiatric Institute, Philadelphia.
Schechter
L E
LE
D000818:Animals; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013239:Stereotyped Behavior / Q000187:drug effects*; D013577:Syndrome; D053778:Thiazolidines; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology
D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D053778:Thiazolidines; D008711:Metergoline; C018406:1-(3-trifluoromethylphenyl)piperazine; C048241:1-(1-naphthyl)piperazine; D013973:Thyrotropin-Releasing Hormone; C021597:pyro(l-alpha-aminoadipyl)-L-histidyl-L-thiazolidine-4-carboxamide; C044643:LY 165163; C015068:1-(3-chlorophenyl)piperazine