RF 9

Ki: 58 nM for NPFF1; 75 nM for NPFF2

RF 9 is a neuropeptide FF receptors antagonist.

Neuropeptide FF (NPFF) has been isolated originally from bovine brain through its cross-reaction with antibodies to the molluscan cardioexcitory peptide FMRF-NH2, which possesses the similar C-terminal sequence. Recent studies shows that NPFF belongs to a neuropeptide family including two G protein-coupled receptors (NPFF1 and NPFF2) and two precursors (pro-NPFFA and pro-NPFFB). Both in vitro and in vivo studies have indicated that NPFF involves in a variety of biological actions.

In vitro: RF9 was found as a potent and selective NPFF receptor antagonist. RF9 was shown to be able to selectively bind to recombinant NPFF1 or NPFF2 receptors expressed in CHO or COS-1 cell and could also in vitro antagonize the agonism induced by NPFF and NPVF in the functional assays [1].

In vivo: Aminal in vivo study showed RF9 (30 nmol) injection failed to induce significant effect, but RF9 could completely antagonize the hypothermia of NPFF after cerebral administration in mice. Additionally, RF9 (30 nmol) co-injected in the third ventricle reduced the hypothermia induced by morphine or nociceptin/orphanin [2].

Clinical trial:N/A

References:
[1] Fang Q,Wang YQ,He F,Guo J,Guo J,Chen Q,Wang R.  Inhibition of neuropeptide FF (NPFF)-induced hypothermia and anti-morphine analgesia by RF9, a new selective NPFF receptors antagonist. Regul Pept.2008 Apr 10;147(1-3):45-51.
[2] Wang YQ,Guo J,Wang SB,Fang Q,He F,Wang R.  Neuropeptide FF receptors antagonist, RF9, attenuates opioid-evoked hypothermia in mice. Peptides.2008 Jul;29(7):1183-90.

Numerical and experimental evaluation of RF shimming in the human brain at 9.4 T using a dual-row transmit array.[Pubmed:24276542]

MAGMA. 2014 Oct;27(5):373-86.

OBJECTIVE: To provide a numerical and experimental investigation of the static RF shimming capabilities in the human brain at 9.4 T using a dual-row transmit array. MATERIALS AND METHODS: A detailed numerical model of an existing 16-channel, inductively decoupled dual-row array was constructed using time-domain software together with circuit co-simulation. Experiments were conducted on a 9.4 T scanner. Investigation of RF shimming focused on B1(+) homogeneity, efficiency and local specific absorption rate (SAR) when applied to large brain volumes and on a slice-by-slice basis. RESULTS: Numerical results were consistent with experiments regarding component values, S-parameters and B1(+) pattern, though the B1(+) field was about 25% weaker in measurements than simulations. Global shim settings were able to prevent B1(+) field voids across the entire brain but the capability to simultaneously reduce inhomogeneities was limited. On a slice-by-slice basis, B1(+) standard deviations of below 10% without field dropouts could be achieved in axial, sagittal and coronal orientations across the brain, even with phase-only shimming, but decreased B1(+) efficiency and SAR limitations must be considered. CONCLUSION: Dual-row transmit arrays facilitate flexible 3D RF management across the entire brain at 9.4 T in order to trade off B1(+) homogeneity against power-efficiency and local SAR.

A new sealed RF-excited CO2 laser for enamel ablation operating at 9.4-mum with a pulse duration of 26-mus.[Pubmed:27006521]

Proc SPIE Int Soc Opt Eng. 2016 Feb 13;9692.

Several studies over the past 20 years have shown that carbon dioxide lasers operating at wavelengths between 9.3 and 9.6-mum with pulse durations near 20-mus are ideal for hard tissue ablation. Those wavelengths are coincident with the peak absorption of the mineral phase. The pulse duration is close to the thermal relaxation time of the deposited energy of a few microseconds which is short enough to minimize peripheral thermal damage and long enough to minimize plasma shielding effects to allow efficient ablation at practical rates. The desired pulse duration near 20-mus has been difficult to achieve since it is too long for transverse excited atmospheric pressure (TEA) lasers and too short for radio-frequency (RF) excited lasers for efficient operation. Recently, Coherent Inc. (Santa Clara, CA) developed the Diamond J5-V laser for microvia drilling which can produce laser pulses greater than 100-mJ in energy at 9.4-mum with a pulse duration of 26-mus and it can achieve pulse repetition rates of 3 KHz. We report the first results using this laser to ablate dental enamel. Efficient ablation of dental enamel is possible at rates exceeding 50-mum per pulse. This laser is ideally suited for the selective ablation of carious lesions.

Acute fasting-induced repression of the hypothalamic-pituitary-gonadal axis is reversed by RF-9 administration in the adult male macaque.[Pubmed:25181419]

Horm Metab Res. 2014 Dec;46(13):927-832.

Recently, hypothalamic RFRP-3 (a mammalian ortholog of avian GnIH) signaling has been proposed as an important negative modulator of the reproductive axis. The current study examined whether repression of reproductive hormonal expression during short-term fasting conditions in higher-order primate is influenced by altered RFRP-3 signaling. Eight intact postpubertal male macaques (Macaca mulatta) were administered a single intravenous bolus of RF-9 (n = 4), a potent and putative RFRP-3 receptor antagonist, or vehicle (n = 4) following a 48-h fasting condition. Intermittent blood samples were collected every 30 min during the 4-h post-bolus period, and blood glucose, plasma cortisol, and testosterone concentrations were measured. Relative to fed conditions, fasting reduced glucose and testosterone levels (p < 0.005) and increased cortisol levels (p < 0.05). Relative to baseline, mean testosterone levels were elevated 150 min after RF-9 (p < 0.05) but not vehicle administration. In addition, elevated mean plasma testosterone levels following RF-9 administration were equivalent to levels observed in normal fed monkeys. These results suggest an important role for RFRP-3 signaling in conveying metabolic state information to the reproductive axis in higher primates.

Neuropeptide FF receptors antagonist, RF9, attenuates opioid-evoked hypothermia in mice.[Pubmed:18406009]

Peptides. 2008 Jul;29(7):1183-90.

The present study used the endpoint of hypothermia to investigate opioid and neuropeptide FF (NPFF) interactions in conscious animals. Both opioid and NPFF systems played important roles in thermoregulation, which suggested a link between opioid receptors and NPFF receptors in the production of hypothermia. Therefore, we designed a study to investigate the relationship between opioid and NPFF in control of thermoregulation in mice. The selective NPFF receptors antagonist RF9 (30nmol) injected into the third ventricle failed to induce significant effect, but it completely antagonized the hypothermia of NPFF (45 nmol) after cerebral administration in mice. In addition, RF9 (30 nmol) co-injected i.c.v. in the third ventricle reduced the hypothermia induced by morphine (5nmol,) or nociceptin/orphanin FQ (N/OFQ) (2 nmol). Neither the classical opioid receptors antagonist naloxone (10 nmol) nor NOP receptor antagonist [Nphe(1)]NC(1-13)NH(2) (7.5 nmol) reduced the hypothermia induced by the central injection of NPFF at dose of 45 nmol. Co-injected with a low dose of NPFF (5 nmol), the hypothermia of morphine (5 nmol) or N/OFQ (2 nmol) was not modified. These results suggest that NPFF receptors activation is required for opioid to produce hypothermia. In contrast, NPFF-induced hypothermia is mainly mediated by its own receptors, independent of opioid receptors in the mouse brain. This interaction, quantitated in the present study, is the first evidence that NPFF receptors mediate opioid-induced hypothermia in conscious animals.

RF9 is a potent and selective Neuropeptide FF receptor antagonist, with Kis of 58±5 and 75±9 nM for hNPFF1R and hNPFF2R, respectively.

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