Disease relevance of Lopac-N-3529

• Hypothermia coincided with USV-suppression, except for NAN-190 and (S)-UH-301 [1].
• NAN-190 slightly, but significantly, suppressed lordosis behavior after either intracerebral or intraperitoneal injection and substantially increased resistive behavior [2].
• Evidence that NAN-190-induced hypotension involves vascular alpha1-adrenoceptor antagonism in the rat [3].
• NAN-190, given alone in similar doses, caused hypothermia and hyperglycemia [4].
• NAN-190 (5-HT1 antagonist; 1 and 10 nmol) increased paw edema, while ritanserin (5-HT2 antagonist; 1 nmol) inhibited paw edema [5].

Psychiatry related information on Lopac-N-3529

• Conversely, ICV injections of the 5-HT(1A) receptor antagonist NAN-190 attenuated the effect of CRH on locomotor activity when given in combination with CRH but had no effect when administered alone [6].
• When administered alone, NAN-190 suppressed REM sleep in the first 2 h, and reduced SWS-2 in the first 4 after administration [7].
• The (5-HT)IA antagonist NAN-190 prevented the stimulus generalization from indorenate to 8-OH-DPAT [8].
• NAN-190 also suppressed selectively NREM sleep slow-wave activity in both fronto-frontal (FF) and FP EEG power spectrum [7].
• NAN-190 was not effective at 0.125 or 1.25 microg any dose but reversed amnesia when given at 1.250 microg simultaneously with both effective doses of 8-OH-DPAT [9].

High impact information on Lopac-N-3529

• This effect is antagonized by the putative 5-HT1A-selective antagonist NAN 190 [10].
• Only NAN-190 (a 5-HT1A antagonist) inhibited the effect of 5-HT, suggesting involvement of this receptor [11].
• This effect was blocked in the substantia nigra by the 5-HT1B/1D receptor antagonist GR-127,935 and in the former two regions by the 5-HT1A antagonist NAN-190 [12].
• In addition, NAN-190, ketanserin, and MDL-72222 were administered to selectively block 5-HT1A, 5-HT2A, and 5-HT3 receptors, respectively [13].
• At a concentration of 10(-4) M at 72 hours the 5HT1A antagonist NAN-190 hydrobromide and the 5-hydroxytryptamine1B antagonist SB224289 HCl (Tocris Laboratories, Bristol, United Kingdom) induced a 20% and 78% inhibitory effect, respectively, on PC3 cell growth compared to that in controls (p < 0.0001) [14].

Chemical compound and disease context of Lopac-N-3529

• The 5-HT1A antagonist, NAN-190 (2 mg/kg, s.c.), blocked both hypothermic and analgesic effects, while systemic administration of the opioid antagonist, naloxone (1 mg/kg, s.c.), did not change the pattern of buspirone-induced hypothermia or analgesia [15].
• However, NAN-190 (1-8 mg/kg) given alone, produced hypothermia and increased the concentration of corticosterone in serum [16].
• WAY 100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide), a highly selective 5-HT(1A) receptor antagonist, increased NAN-190-induced hypotension (p<0.05) [3].
• In contrast, smaller doses of NAN-190 had a significant effect, whereas higher doses (2.5-10.0 mg/kg) decreased locomotor activity and other active behaviours, a profile similar to that produced by the alpha1-adrenoceptor antagonist prazosin (2.5 mg/kg), which also inhibited open arm activity [17].
• Methamphetamine (1.5 mg/kg, i.p) produced a significant increase in locomotor activity, which was significantly antagonized by NAN-190 at a dose of 4 mg/kg, i.p. NAN-190 did not alter the antinociceptive activity of mice when it was administered alone [18].

Biological context of Lopac-N-3529

• The i.v. injection of NAN-190 (1-300 micro/kg) dose-dependently decreased blood pressure (p<0.001), while heart rate was not significantly modified compared to saline-treated, anaesthetized adult rats [3].
• Both compounds caused a dose-related increase in the intensity of the '5-HT syndrome'. After pretreatment with NAN 190 (100 micrograms/kg s.c.) the increases in heart rate, respiratory rate and symptoms of the '5-HT syndrome' were significantly reduced but the decreases in systolic and diastolic pressure were additive [19].
• In this respect NAN-190 was a 250-fold more potent antagonist than prazosin (IC50 = 49 nM) [20].
• The increased defecation induced by 8-OH-DPAT could be antagonised by pindolol and NAN-190 [21].
• Rat pups were treated with parachloroamphetamine (PCA), 5,7-DHT or the 5-HT1a receptor antagonist NAN-190 [22].

Anatomical context of Lopac-N-3529

• Eight of the 14 antagonists tested were effective against 5-HT(apAC) in CNS membranes with the following rank order of potency: methiothepin > metergoline approximately fluphenazine > clozapine > cyproheptadine approximately risperidone approximately ritanserin > NAN-190 [23].
• The 5-HT1A mixed agonist-antagonist (1-(2-methoxyphenyl) 4-[4-(2-pthalimido)butyl]piperazine, i.p. NAN-190) attenuated the discriminative stimulus effects of 8-OH-DPAT injected i.p. (0.1 mg/kg), into the DRN (10 micrograms) or into the hippocampus (2 x 10 micrograms).(ABSTRACT TRUNCATED AT 250 WORDS)[24]
• Although bilateral injections of 8-OH-DPAT (5.6 nmol/0.4 microl) or NAN-190 (5.6 nmol and 10 nmol/0.4 microl) into the amygdala did not alter OAIA, increased anxiety was observed in the EPM [25].
• Dose-dependent attenuation was also obtained with ketaserin (0. 01-10 mg/kg), cyproheptadine (0.01-10 mg/kg), pindolol (0.1-100 mg/kg) and NAN-190 (0.1-100 mg/kg), but not with 0.01 to 10 mg/kg of ICS205-930 or M-840, and the activities were significantly correlated with the binding affinities for serotonin2 receptor on the rat cerebral cortex [26].
• The growth-inhibition effect of a 5-HT1A antagonist (NAN-190) on PC cell lines was studied using a bromodeoxyuridine (BrdU) assay [27].

Associations of Lopac-N-3529 with other chemical compounds

• The effect of 5-HT was blocked by the 5-HT1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide (NAN-190) but not by ketanserin, a 5-HT2A/2C antagonist [28].
• An antagonist of 5-HT1A receptor, NAN-190, eliminates the effect of serotonin and buspirone on AA and NO/cGMP liberation [29].
• Further, STFs evoked by LY 165,163 in the presence of apomorphine were abolished by the 5-HT1A antagonists (-)-alprenolol, BMY 7378 and NAN-190 [30].
• DAU 6215 did not antagonize the 5-HT1A-induced membrane hyperpolarization and conductance increase, a response that was blocked by the selective 5-HT1A antagonist NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phtalamido)butyl- piperazine) [31].
• In comparison, SDZ 216-525 is reported to have slightly higher affinity for the 5-HT1A site than 8-OH-DPAT and NAN-190 [32].

Gene context of Lopac-N-3529

• Systemic administration of the selective 5-HT1A antagonist NAN-190 immediately after training markedly-and dose-dependently-facilitated retention in the passive-avoidance task; enhanced retention was time-dependent and was not attributable to variations in wattages of shock received by animals [33].
• Consistent with these results, IGF-I was significantly decreased when mandibular mesenchymal cells were grown in serum-containing medium (which contains micromolar amounts of 5-HT from fetal calf serum) and treated with 10(-8) M antagonist selective for the 5-HT(1A) or 5-HT(4) receptor subtype (NAN-190 on SDZ-205,557) [34].
• The mechanisms responsible for the NAN-190-induced hypothermia and secretion of corticosterone are still unknown, though stimulation of 5-HT1A receptors (either effect), 5-HT2 receptors and alpha 1- and alpha 2-adrenoceptors (corticosterone response) seems to be excluded [16].
• The effect of systemically applied 8-OH-DPAT was abolished by i.p. injection of the 5-HT1A receptor antagonist, NAN-190, administered 20 min before the 8-OH-DPAT [35].
• New arylpiperazines related to buspirone, gepirone and NAN-190 were designed and screened in silico for their 5-HT(1A) affinity and potential sites of metabolism by human cytochrome p450 (CYP3A4) [36].

Analytical, diagnostic and therapeutic context of Lopac-N-3529

• Microinjections of NAN-190, a 5-HT-1A receptor blocker, enhanced hypoxic augmentation resulting in apneustic prolongation of inspiratory bursts [37].
• Intrathecal injection of the 5-HT(1A) receptor antagonist NAN-190 (0.2 mM) alone did not influence Adelta- and C-responses and post-discharge of WDR neurons in normal rats [38].
• Following perfusion of 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine (NAN-190; 10 microM), which is a selective 5-HT1A antagonist, the effect of 8-OH-DPAT was totally abolished, whereas CGS-12066B decreased extracellular ACh levels [39].
• However, NAN-190 also increased NMDA-induced behaviour in the control group, suggesting that a tonic inhibition of this behaviour, mediated by the 5-HT1A receptor, may exist [40].
• However, the EEG power spectral density and REM sleep suppressive effects of NAN-190 were both augmented [7].

References