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Chemical Compound Review

TFMPP     1-[3-(trifluoromethyl) phenyl]piperazine...

Synonyms: PubChem8594, SureCN720648, AC-806, ACMC-209v9p, ACN-S002540, ...
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Disease relevance of NSC 128882


Psychiatry related information on NSC 128882

  • In tests of stimulus generalization using rats trained to discriminate TFMPP (ED50 = 0.17 mg/kg) from saline, 3a was found to be nearly equipotent (ED50 = 0.22 mg/kg) with the training drug [6].
  • 1-(3-chlorophenyl)piperazine (mCPP) and 1-[3-(trifluoromethyl)phenyl]piperazine (TFMPP) (0.1-1.0 mg/kg) reduce total interaction time in a rat social interaction test under low light familiar conditions and its following components; grooming, following, crawling over, fighting, sniffing [7].
  • Present data indicate that serotonergic postsynaptic receptors mediate both the inhibitory and the facilitatory actions of TFMPP or 8-OH-DPAT in copulation [8].

High impact information on NSC 128882

  • The 5HT1B receptor agonists TFMPP and CGS 12066A, administered systemically, inhibited light-induced phase shifts of the circadian activity rhythm in a dose-dependent manner at phase delay and phase advance time points [9].
  • The 5-HT1B/2C receptor agonist TFMPP (trifluorometaphenylpiperazine) stimulated USV at a low dose at the cold plate and suppressed USV at a high dose under both conditions [10].
  • In an acute study TFMPP reduced overall brain 5-HT synthesis, in the dorsal and median raphe, and in almost all of their projection areas, with the exception of the parietal, sensory-motor, and frontal cortices, the accumbens nucleus, and the caudate [11].
  • The intravenous administration of the selective 5-HT1A agonist 8-OH-DPAT (30 micrograms/kg) and the 5-HT1 agonist TFMPP (0.5 mg/kg) reduced the 5-hydroxyindole signal by 23% and 18%, respectively [12].
  • The 5-HT2 antagonist ketanserin had no effect on the TFMPP-induced decrease in respiratory activity [13].

Chemical compound and disease context of NSC 128882

  • The role of 5-HT (serotonin) in regulating lordosis was investigated by combining peripheral administration of the 5-HT agonists 8-OH-DPAT (8-hydroxy-2-[di-N-propylamino]tetralin) or TFMPP (1-[m-trifluoromethylphenyl]piperazine), with intrahypothalamic application of the 5-HT neurotoxin 5,7-DHT (5,7-dihydroxytryptamine) [14].
  • Similarly to imipramine-like drugs, TFMPP antagonized oxotremorine-induced hypothermia and was active in the behavioural despair test [15].

Biological context of NSC 128882

  • The IC50 for 5-CT was 3.6 +/- 0.5 nM, for 8-OH-DPAT was 0.4 +/- 0.04 microM, for TFMPP was 0.93 +/- 0.3 microM and for methysergide was 21.8 +/- 3.0 nM [16].
  • In contrast to the effects of 8-OH-DPAT and TFMPP, DOI (0.3-100 micrograms) produced an increase in blood pressure without any change in heart rate [3].
  • It is concluded that there are sex differences in the effects of TFMPP and MCPP on copulatory behavior in the rat [1].
  • MK-212 (fractional efficacy = 1.1) and (-)DOM (0.77) were full agonists, while mCPP (0.72), LSD (0.27), quipazine (0.24), and TFMPP (0.22) were partial agonists with respect to the stimulation of PI hydrolysis at the 5-HT2C receptor [17].
  • The present experiments served to compare the effects of the 3 5-HT1 agonists, 8-OH-DPAT, 5-MeODMT and TFMPP on the blood pressure and heart rate of normotensive anaesthetized rats [18].

Anatomical context of NSC 128882

  • A decrease in the amplitude of the recurrent laryngeal and phrenic nerve signals was observed after application of the highest dose of TFMPP [3].
  • 3 Stimulation of the nucleus tractus solitarius (NTS) induced inhibitory synaptic currents that were reduced in amplitude by application of the 5-HT1A receptor agonist 8-OHDPAT (1 microM) or the 5-HT1A/1B receptor agonist TFMPP (1 microM) in 61% and 52% of gastric- and intestinal-projecting neurones, respectively [19].
  • As previously described in the hamster, a mixed 5-HT(1A/1B) receptor agonist, 1-[3-(trifluoromethyl)phenyl]-piperazine hydrochloride (TFMPP), reduced the amplitude of glutamatergic excitatory postsynaptic currents (EPSCs) evoked by selectively stimulating the optic nerve of wild-type mice [20].
  • Pretreatment with 6-hydroxydopamine (100 micrograms, intrathecal) for 7-10 days, which reduced spinal cord levels of noradrenaline by 87%, inhibited the action of TFMPP (and 5-HT), but not CGS 12066B or DOI [21].
  • TFMPP, a 5HT1B receptor agonist, inhibits light-induced phase shifts of the circadian activity rhythm and c-Fos expression in the mouse suprachiasmatic nucleus [22].

Associations of NSC 128882 with other chemical compounds

  • Repeated treatment with RU 24969 (5 mg/kg, daily, for 3 days) reduced the effect of TFMPP and that of other 5-HT1B agonists (CGS 120 66B, m-CPP, RU 24969) [23].
  • Four-day-old (P4) and 21-22-day-old (P21-22) rat pups received an intracisternal injection of either ACTH1-16NH2 or saline followed by a subcutaneous (SC) injection of saline, the serotonergic (5HT)1A agonists 8-OH-DPAT or ipsapirone, the 5HT1B agonist TFMPP or the 5HT2 agonist DOI [24].
  • Previous studies found that the degree of substitution of the 5-HT1B/2C agonist TFMPP (m-trifluoromethylphenylpiperazine) depended on the training dose of ethanol [25].
  • The effect of 1-[3-(trifluoromethyl)phenyl] piperazine (TFMPP), a 5-hydroxytryptamine (5-HT) receptor agonist, on the threshold for maximal electroconvulsions was studied in mice [26].
  • 4. The effects of 5-HT were mimicked by the 5-HT1B receptor agonists 1-[3-(trifluoromethyl)phenyl]-piperazine (TFMPP) and 7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1,2-a]-quinoxaline maleate and antagonized by the 5-HT1B receptor antagonist (-)-pindolol [27].

Gene context of NSC 128882

  • RESULTS: The 5-HT1A agonists (+)8-OH-DPAT (0.01-0.1 mg/kg) and flesinoxan (0.3-1.0 mg/kg), the selective 5-HT1B agonist CP-94,253 (0.03-30.0 mg/kg), and the mixed 5-HT1B/2C receptor agonist TFMPP (0.1-10.0 mg/kg) dose-dependently reduced USVs [28].
  • The agonist was negligibly effective in a 5-HT1B receptor knockout mouse, suggesting minimal contribution of 5-HT1A receptors to the TFMPP-induced reduction in the amplitude of the optic nerve-evoked EPSC [20].
  • However, methylsergide (5-HT1/5-HT2 antagonist) and (-)-cyanopindolol (5-HT1B antagonist) antagonized the TFMPP-induced respiratory rate decrease [13].
  • This action appears to be due to activation of a 5-HT1-like receptor as it is mimicked by some 5-HT1 receptor ligands (mCPP, TFMPP and 5-Me-O-DMT), but not by DOI (5-HT2) or 2-Me-5-HT (5-HT3) [29].
  • Systemic administration of TFMPP prior to light stimulation significantly attenuated light-induced phase shifts of the circadian activity rhythm and Fos expression in the SCN [22].

Analytical, diagnostic and therapeutic context of NSC 128882


  1. Sex differences in the effects of 1-(m-trifluoromethylphenyl) piperazine and 1-(m-chlorophenyl) piperazine on copulatory behavior in the rat. Mendelson, S.D., Gorzalka, B.B. Neuropharmacology (1990) [Pubmed]
  2. The effects of paroxetine given repeatedly on the 5-HT receptor subpopulations in the rat brain. Maj, J., Bijak, M., Dziedzicka-Wasylewska, M., Rogoz, R., Rogóz, Z., Skuza, G., Tokarski, T. Psychopharmacology (Berl.) (1996) [Pubmed]
  3. Characterization of the effects of activation of ventral medullary serotonin receptor subtypes on cardiovascular activity and respiratory motor outflow to the diaphragm and larynx. King, K.A., Holtman, J.R. J. Pharmacol. Exp. Ther. (1990) [Pubmed]
  4. Efficacy of administration of dexfenfluramine and phentermine, alone and in combination, on ingestive behavior and body weight in rats. Roth, J.D., Rowland, N.E. Psychopharmacology (Berl.) (1998) [Pubmed]
  5. Effect of chronic treatment with TFMPP, a 5-HT1 receptor agonist, on food intake, weight gain, plasma insulin and neuropeptide mRNA expression in obese Zucker rats. Rouru, J., Pesonen, U., Isaksson, K., Huupponen, R., Koulu, M. Eur. J. Pharmacol. (1993) [Pubmed]
  6. Synthesis and evaluation of phenyl- and benzoylpiperazines as potential serotonergic agents. Lyon, R.A., Titeler, M., McKenney, J.D., Magee, P.S., Glennon, R.A. J. Med. Chem. (1986) [Pubmed]
  7. Anxiogenic-like effects of mCPP and TFMPP in animal models are opposed by 5-HT1C receptor antagonists. Kennett, G.A., Whitton, P., Shah, K., Curzon, G. Eur. J. Pharmacol. (1989) [Pubmed]
  8. Role of presynaptic serotonergic receptors on the mechanism of action of 5-HT1A and 5-HT1B agonists on masculine sexual behaviour: physiological and pharmacological implications. Fernández-Guasti, A., Escalante, A. J. Neural Transm. Gen. Sect. (1991) [Pubmed]
  9. 5HT1B receptor agonists inhibit light-induced phase shifts of behavioral circadian rhythms and expression of the immediate-early gene c-fos in the suprachiasmatic nucleus. Pickard, G.E., Weber, E.T., Scott, P.A., Riberdy, A.F., Rea, M.A. J. Neurosci. (1996) [Pubmed]
  10. Ultrasonic vocalizations in rat pups: effects of serotonergic ligands. Olivier, B., Molewijk, H.E., van der Heyden, J.A., van Oorschot, R., Ronken, E., Mos, J., Miczek, K.A. Neuroscience and biobehavioral reviews. (1998) [Pubmed]
  11. Effects of serotine receptors agonists, TFMPP and CGS12066B, on regional serotonin synthesis in the rat brain: an autoradiographic study. Tohyama, Y., Yamane, F., Fikre Merid, M., Blier, P., Diksic, M. J. Neurochem. (2002) [Pubmed]
  12. 5-HT1D receptors regulate 5-HT release in the rat raphe nuclei. In vivo voltammetry and in vitro superfusion studies. Piñeyro, G., de Montigny, C., Blier, P. Neuropsychopharmacology (1995) [Pubmed]
  13. 5-HT1A and 5-HT1B agonists play a differential role on the respiratory frequency in rats. Edwards, E., Whitaker-Azmitia, P.M., Harkins, K. Neuropsychopharmacology (1990) [Pubmed]
  14. 5,7-DHT facilitated lordosis: effects of 5-HT agonists. Aiello-Zaldivar, M., Luine, V., Frankfurt, M. Neuroreport (1992) [Pubmed]
  15. Psychopharmacological profile of 1-(m-(trifluoromethyl) phenyl) piperazine (TFMPP). Frances, H. Pharmacol. Biochem. Behav. (1988) [Pubmed]
  16. Inhibition of reflex responses of neonate rat lumbar spinal cord by 5-hydroxytryptamine. Crick, H., Wallis, D.I. Br. J. Pharmacol. (1991) [Pubmed]
  17. 5-HT2C receptor-mediated phosphoinositide turnover and the stimulus effects of m-chlorophenylpiperazine. Fiorella, D., Helsley, S., Rabin, R.A., Winter, J.C. Psychopharmacology (Berl.) (1995) [Pubmed]
  18. Comparison of effects of some 5-HT1 agonists on blood pressure and heart rate of normotensive anaesthetized rats. Dabire, H., Cherqui, C., Fournier, B., Schmitt, H. Eur. J. Pharmacol. (1987) [Pubmed]
  19. Characterization of the in vitro effects of 5-hydroxytryptamine (5-HT) on identified neurones of the rat dorsal motor nucleus of the vagus (DMV). Browning, K.N., Travagli, R.A. Br. J. Pharmacol. (1999) [Pubmed]
  20. Serotonergic modulation of retinal input to the mouse suprachiasmatic nucleus mediated by 5-HT1B and 5-HT7 receptors. Smith, B.N., Sollars, P.J., Dudek, F.E., Pickard, G.E. J. Biol. Rhythms (2001) [Pubmed]
  21. Noradrenergic mediation of spinal antinociception by 5-hydroxytryptamine: characterization of receptor subtypes. Sawynok, J., Reid, A. Eur. J. Pharmacol. (1992) [Pubmed]
  22. TFMPP, a 5HT1B receptor agonist, inhibits light-induced phase shifts of the circadian activity rhythm and c-Fos expression in the mouse suprachiasmatic nucleus. Pickard, G.E., Rea, M.A. Neurosci. Lett. (1997) [Pubmed]
  23. Tolerance to the behavioural effect of serotonergic (5-HT1B) agonists in the isolation-induced social behavioural deficit test. Frances, H., Monier, C. Neuropharmacology (1991) [Pubmed]
  24. ACTH-induced behaviors and their modulation by serotonergic agonists differ in neonatal and weanling rat pups. Kirstein, C.L., Traber, J., Gispen, W.H., Spear, L.P. Psychopharmacology (Berl.) (1990) [Pubmed]
  25. Characterization of the ethanol-like discriminative stimulus effects of 5-HT receptor agonists as a function of ethanol training dose. Grant, K.A., Colombo, G., Gatto, G.J. Psychopharmacology (Berl.) (1997) [Pubmed]
  26. Role of 5-hydroxytryptamine receptor subtypes in the 1-[3-(trifluoromethyl)phenyl] piperazine-induced increase in threshold for maximal electroconvulsions in mice. Przegaliński, E., Baran, L., Siwanowicz, J. Epilepsia (1994) [Pubmed]
  27. Effects of 5-HT on thalamocortical synaptic transmission in the developing rat. Rhoades, R.W., Bennett-Clarke, C.A., Shi, M.Y., Mooney, R.D. J. Neurophysiol. (1994) [Pubmed]
  28. Distress vocalizations in maternally separated mouse pups: modulation via 5-HT(1A), 5-HT(1B) and GABA(A) receptors. Fish, E.W., Sekinda, M., Ferrari, P.F., Dirks, A., Miczek, K.A. Psychopharmacology (Berl.) (2000) [Pubmed]
  29. Interactions of descending serotonergic systems with other neurotransmitters in the modulation of nociception. Sawynok, J., Reid, A. Behav. Brain Res. (1996) [Pubmed]
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