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Serotonin pp 359-368 | Cite as

Structure-Activity Relationships in the Actions of 1-Phenyl-Piperazines on Brain Serotonin Receptors

  • Ray W. Fuller
  • Norman R. Mason
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 133)

Abstract

Several compounds containing a 1-phenyl-piperazine moiety have been reported to interact with central serotoninergic systems. For example, trazodone, 2-(3-[4-(m-chlorophenyl)-1piperazinyl]propyl)-S-triazolo-[4,3-a]pyridin-3[2H]-one (Fig. 1), has been variously described as a serotonin uptake inhibitor, agonist, and antagonist (Silvestrini et al, 1968; Garattini et al, 1976; Maj et al, 1979). Mepiprazole, 1-(m-chlorophenyl)-4[2-(5-methyl-3-pyrazolyl)-ethyl]-piperazine (Fig. 1), has been claimed to increase serotonin concentration at the receptor site by a combination of neuronal uptake inhibition and release (Placheta et al, 1975), and Fuxe et al (1976) have suggested that mepiprazole causes extragranular release of serotonin stores. Related compounds with a simpler structure have also been studied. For example, 1-(m-chlorophenyl)-piperazine, a possible metabolite of trazodone (and of mepiprazole), was observed to inhibit serotonin uptake more potently than trazodone (Garattini et al, 1976). l-(m-Trifluoromethylphenyl)-piperazine has been reported to have serotonin agonist activity (Fuller et al, 1978; Fuller and Clemens, 1979). Quipazine and MK-212 are serotonin agonists (Rodriguez et al, 1973; Clineschmidt et al, 1977) that are 1-aryl-piperazines but not 1-phenyl-piperazines (see Fig. 1). Because of these reports, we have undertaken a study of various substituted 1-phenyl-piperazines and related compounds to determine their ability to act directly on serotonin receptors as indicated by their competition with 3H-serotonin for binding to membranes from rat brain in vitro. These effects and others of some 1-phenyl-piperazines are described herein.

Keywords

Methyl Orange Serotonin Receptor Serotonin Uptake Serum Corticosterone Prolactin Concentration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • Ray W. Fuller
    • 1
  • Norman R. Mason
    • 1
  1. 1.The Lilly Research LaboratoriesEli Lilly and CompanyIndianapolisUSA

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