Disease relevance of p-MPPI

• When given i.p., p-MPPI and p-MPPF dose-dependently antagonized the hypothermia induced by 8-hydroxy-2- (di-n-propylamino)tetralin (8-OH-DPAT) (0.5 mg/kg), with approximate ID50 of 5 and 3 mg/kg, respectively [1].
• Further, the 5-HT reuptake inhibitor fluoxetine, the 5-HT(1B/1C) receptor agonist TFMPP, the 5-HT synthesis inhibitor p-CPA, the selective 5-HT1A receptor antagonist p-MPPI, the 5-HT(1A/1B) receptor antagonist pindolol and the 5-HT3 receptor antagonist LY 278, 584 had no effect on NECA-induced catalepsy [2].

Psychiatry related information on p-MPPI

• The behavioural profile of p-MPPI is contrasted with those previously obtained with other 5-HT1A receptor ligands (agonists, partial agonists and antagonists), and it is suggested that 5-HT1A receptor antagonists may possess therapeutic advantages in anxiety disorders [3].
• The selective 5-HT(1A) antagonist 4-(2'-methoxy-phenyl)-1-[2'-(n-2"-pyridinyl)-p-iodobenzamido]-ethyl-piperazine (p-MPPI) induces a dose-related decrease in REM sleep [4].
• These results indicate that p-MPPI is an effective 5-HT1A receptor antagonist in vivo with no intrinsic activity. p-MPPI may prove to be a useful pharmacological tool for studying 5-HT1A receptors and their involvement in anxiety and affective disorders [5].

High impact information on p-MPPI

• Thus, using G protein activation as an index of receptor activity, p-MPPF was classified as a neutral antagonist, p-MPPI as a partial inverse agonist, and spiperone as essentially a full inverse agonist [6].
• Isoindol-1-one analogues of 4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridyl)-p-iodobenzamido]ethyl]pipera zine (p-MPPI) as 5-HT1A receptor ligands [7].
• Paroxetine (5 mg/kg s.c.) plus p-MPPI (8.5 mg/kg s.c.) also increased Arc mRNA but p-MPPI itself elevated Arc mRNA in many regions [8].
• Anxiolytic-like profile of p-MPPI, a novel 5HT1A receptor antagonist, in the murine elevated plus-maze [3].
• Neither p-MPPI nor p-MPPF (10 mg/kg) given alone significantly altered the ratio of 5-HIAA/5-HT in the hippocampus or striatum [1].

Chemical compound and disease context of p-MPPI

• The inhibitory effect caused by a fixed dose of p-MPPI (6 mg/kg) or p-MPPF (3 mg/kg) was surmounted by higher doses of 8-OH-DPAT. p-MPPI and p-MPPF also attenuated the hypothermia induced by gepirone [1].

Biological context of p-MPPI

• However, the significant increase in Kd at a higher concentration of NCS-MPP (50 nM) indicated that there may be a secondary alkylation site, which may not be directly involved in p-MPPI binding to receptors; nevertheless, it would lead to an increased Kd value [9].
• Pretreatment with p-MPPI reduced or blocked the effect of the 5-HT1A receptor agonist 8-OH-DPAT on two responses mediated by postsynaptic 5-HT1A receptors, reduction of body temperature and the 5-HT behavioral syndrome [5].

Anatomical context of p-MPPI

• The effects of the putative 5-HT1A receptor antagonist 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzam ide (p-MPPI) were examined on the activity of serotonergic dorsal raphe nucleus neurons in freely moving cats [10].
• Also, p-MPPI (5 and 10 mg/kg i.p.) reduced the effect of 8-OH-DPAT on locomotion and partially or completely antagonized hindlimb abduction and flat body posture [4].
• By pretreatment with the selective 5-HT1A receptor antagonist p-MPPI (3 mg/kg, i.p.), systemic treatment of clozapine (10 mg/kg, i.p.) significantly increased 5-HT efflux in the prefrontal cortex [11].

Associations of p-MPPI with other chemical compounds

• Thus, it was concluded that WAY 100635, NAD-299, NDL-249, and p-MPPI all fulfill criteria as 5-HT1A receptor antagonists lacking intrinsic efficacy in the dorsal raphe system [12].
• The behavioral effects of other compounds with 5-HT1A receptor activities (4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-pyridinyl-benz ami de hydrochloride (p-MPPI): (-)-1-(1H-indol-4-yloxy)-3-(cyclohexylamino)-2-propanol maleate ((-)-LY206130); racemic pindolol and idazoxan) also differed between groups [13].
• A potential 5-HT1A receptor antagonist, p-MPPI, 4-(2'-methoxy-)phenyl-1-[2'-(n-2"-pyridinyl)-p-iodobenzamido-]ethy l- piperazine, was developed [14].

Gene context of p-MPPI

• RESULTS: Among the compounds tested, only 4-(2'-methoxy-phenyl)-1-[2'-(n-2"-pyridinyl)-p-iodobenzamido]-ethyl-piperazine (p-MPPI) and methiothepin showed nanomolar affinity for the 5-HT1A receptors, the former being a neutral antagonist and the latter an inverse agonist in the [35S]GTPgammaS binding model [15].
• In developing radioiodinated antagonists for in vivo imaging of 5-HT1A receptors with SPECT, a series of new arylpiperazine benzamido derivatives, including 4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridyl)-p-iodobenzamido]ethyl]p iperazine (p-MPPI, 31) (Kd = 0.36 nM), as potential ligands for 5-HT1A receptors were reported previously [7].
• The effect of a selective 5-HT(1A) antagonist, 4-(2'-methoxy-)phenyl-1-[2'-(N-2"-pyridinyl)-p-iodobenzamino-]ethyl-piperazine (p-MPPI), on acute ethanol-induced hypothermia, sleep and suppression of acoustic startle reflex in C3H/He mice and Wistar rats was studied [16].

Analytical, diagnostic and therapeutic context of p-MPPI

• Perfusion of 100 microM of p-MPPI decreased total transition type sleep (TRANS) but the effect on REM sleep did not reach significance [17].
• In the present study, a blockade by microdialysis perfusion of 10 microM and 100 microM of p-MPPI for 7 h into the DRN in freely behaving rats influenced vigilance state only to a small extent [17].
• Intravenous injection of low doses of p-MPPI and methiothepin induced a dose-dependent disappearance of isovolumic bladder contractions in anaesthetized rats (> 10 min) [15].

References