Disease relevance of NSC 128882

• Peripheral administrations of TFMPP (0.2- 1 mg/kg) or MCPP (1 mg/kg) facilitated lordosis behavior in female rats treated with estradiol benzoate, and had no effects in females primed with estradiol benzoate and progesterone [1].
• Either of the antidepressants given repeatedly antagonized TFMPP-induced hyperthermia (another putative 5-HT2C effect) [2].
• TFMPP (10-1000 micrograms) also produced a dose-dependent hypotension and bradycardia [3].
• Additionally, the effects of the 5-HT2C agonist 1-[3-(trifluoromethyl)-phenyl]piperazine (TFMPP) alone and in combination with PHEN on food intake and body weight were assessed [4].
• The present investigation was performed to study the chronic effects of TFMPP on food intake and weight gain in genetically obese Zucker rats [5].

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

• Anxiogenic-like effects of mCPP and TFMPP in animal models are opposed by 5-HT1C receptor antagonists [7].
• Chronic TFMPP administration significantly reduced the density of 5-HT2 receptors, as measured by quantitative receptor autoradiography, in the claustrum and cerebral cortex, but not 5-HT1C receptor density in the choroid plexus [5].

References