Phosphate is a major intracellular anion in mammals. Hydrogen phopshate is a protonated form of phosphate. In serum, phosphate exists in two forms, dihydrogen phosphate (H2PO4) and its salt, mono-hydrogen phosphate (HPO4). At the physiologic pH of 7.40, the pK of H2PO4 is 6.8 and the ratio of HPO4 to H2PO4 is 4:1. Altered level of phosphate can be an indicator of various disorders, such as chronic renal failure, hypoparathyroidism, familial intermittent hyperphosphatemia, endocrine disorders, hyperthyroidism, acromegaly, juvenile hypogonadism, etc. These disorders may lead to either hyper- or hypophosphatemia, which can be caused by cellular shifts of phosphate. Patients with hypophosphatemia can be treated with dietary phosphate supplements (potassium phosphate, for example).

AMG-517, a potent and selective vanilloid receptor (VR1) antagonist, was in clinical trials with Amgen for the treatment of pain. AMG 517 inhibits CAP- (500 nM), acid- (pH 5.0), or heat-(45 °C) induced 45Ca2+ influx into human TRPV1-expressing CHO Cells with IC50 of 0.76 nM, 0.62 nM and 1.3 nM. AMG-517 blocks capsaicin-, proton-, and heat-induced inward currents in TRPV1-expressing cells similarly. AMG-517 inhibits native TRPV1 activation by capsaicin in rat dorsal root ganglion neurons with an IC50 value of 0.68 nM. Oral administration of AMG-517 produces a dose-dependent increase in plasma concentrations, it also produces a dose-dependent decrease in the number of flinches induced by capsaicin treatment. The minimally effective dose (MED), based on a statistically significant difference in number of flinches from the vehicle versus capsaicin-administered group, is 0.3 mg/kg for AMG 517. The corresponding plasma concentrations are 90 to 100 ng/mL for AMG-517. AMG-517 (3 mg/kg) exhibits significant reductions in capsaicin-induced flinch up to 24 h after dosing. AMG 517 blocks thermal hyperalgesia in CFA model of pain. Unfortunately, clinical studies of AMG-517 were discontinued due to the hyperthermia observed after exposure to single and multiple doses.

Phosphate is a major intracellular anion in mammals. Hydrogen phopshate is a protonated form of phosphate. In serum, phosphate exists in two forms, dihydrogen phosphate (H2PO4) and its salt, mono-hydrogen phosphate (HPO4). At the physiologic pH of 7.40, the pK of H2PO4 is 6.8 and the ratio of HPO4 to H2PO4 is 4:1. Altered level of phosphate can be an indicator of various disorders, such as chronic renal failure, hypoparathyroidism, familial intermittent hyperphosphatemia, endocrine disorders, hyperthyroidism, acromegaly, juvenile hypogonadism, etc. These disorders may lead to either hyper- or hypophosphatemia, which can be caused by cellular shifts of phosphate. Patients with hypophosphatemia can be treated with dietary phosphate supplements (potassium phosphate, for example).

Phosphate is a major intracellular anion in mammals. Hydrogen phopshate is a protonated form of phosphate. In serum, phosphate exists in two forms, dihydrogen phosphate (H2PO4) and its salt, mono-hydrogen phosphate (HPO4). At the physiologic pH of 7.40, the pK of H2PO4 is 6.8 and the ratio of HPO4 to H2PO4 is 4:1. Altered level of phosphate can be an indicator of various disorders, such as chronic renal failure, hypoparathyroidism, familial intermittent hyperphosphatemia, endocrine disorders, hyperthyroidism, acromegaly, juvenile hypogonadism, etc. These disorders may lead to either hyper- or hypophosphatemia, which can be caused by cellular shifts of phosphate. Patients with hypophosphatemia can be treated with dietary phosphate supplements (potassium phosphate, for example).

Phosphate is a major intracellular anion in mammals. Hydrogen phopshate is a protonated form of phosphate. In serum, phosphate exists in two forms, dihydrogen phosphate (H2PO4) and its salt, mono-hydrogen phosphate (HPO4). At the physiologic pH of 7.40, the pK of H2PO4 is 6.8 and the ratio of HPO4 to H2PO4 is 4:1. Altered level of phosphate can be an indicator of various disorders, such as chronic renal failure, hypoparathyroidism, familial intermittent hyperphosphatemia, endocrine disorders, hyperthyroidism, acromegaly, juvenile hypogonadism, etc. These disorders may lead to either hyper- or hypophosphatemia, which can be caused by cellular shifts of phosphate. Patients with hypophosphatemia can be treated with dietary phosphate supplements (potassium phosphate, for example).

Phosphate is a major intracellular anion in mammals. Hydrogen phopshate is a protonated form of phosphate. In serum, phosphate exists in two forms, dihydrogen phosphate (H2PO4) and its salt, mono-hydrogen phosphate (HPO4). At the physiologic pH of 7.40, the pK of H2PO4 is 6.8 and the ratio of HPO4 to H2PO4 is 4:1. Altered level of phosphate can be an indicator of various disorders, such as chronic renal failure, hypoparathyroidism, familial intermittent hyperphosphatemia, endocrine disorders, hyperthyroidism, acromegaly, juvenile hypogonadism, etc. These disorders may lead to either hyper- or hypophosphatemia, which can be caused by cellular shifts of phosphate. Patients with hypophosphatemia can be treated with dietary phosphate supplements (potassium phosphate, for example).