A potent inhibitor of membrane metalloendopeptidase (ENKEPHALINASE). Thiorphan potentiates morphine-induced ANALGESIA and attenuates naloxone-precipitated withdrawal symptoms.
Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA Antigen), an important marker in the diagnosis of human acute lymphocytic leukemia. There is no relationship with CALLA PLANT.
Sulfhydryl acylated derivative of GLYCINE.
A mammalian neuropeptide of 10 amino acids that belongs to the tachykinin family. It is similar in structure and action to SUBSTANCE P and NEUROKININ B with the ability to excite neurons, dilate blood vessels, and contract smooth muscles, such as those in the BRONCHI.
Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).
Proteins which contain carbohydrate groups attached covalently to the polypeptide chain. The protein moiety is the predominant group with the carbohydrate making up only a small percentage of the total weight.
One of the endogenous pentapeptides with morphine-like activity. It differs from LEU-ENKEPHALIN by the amino acid METHIONINE in position 5. Its first four amino acid sequence is identical to the tetrapeptide sequence at the N-terminal of BETA-ENDORPHIN.
A class of cell surface receptors for tachykinins that prefers neurokinin A; (NKA, substance K, neurokinin alpha, neuromedin L), neuropeptide K; (NPK); or neuropeptide gamma over other tachykinins. Neurokinin-2 (NK-2) receptors have been cloned and are similar to other G-protein coupled receptors.
A family of biologically active peptides sharing a common conserved C-terminal sequence, -Phe-X-Gly-Leu-Met-NH2, where X is either an aromatic or a branched aliphatic amino acid. Members of this family have been found in mammals, amphibians, and mollusks. Tachykinins have diverse pharmacological actions in the central nervous system and the cardiovascular, genitourinary, respiratory, and gastrointestinal systems, as well as in glandular tissues. This diversity of activity is due to the existence of three or more subtypes of tachykinin receptors.
An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses.
A 21-amino acid peptide that circulates in the plasma, but its source is not known. Endothelin-3 has been found in high concentrations in the brain and may regulate important functions in neurons and astrocytes, such as proliferation and development. It also is found throughout the gastrointestinal tract and in the lung and kidney. (N Eng J Med 1995;333(6):356-63)
One of the endogenous pentapeptides with morphine-like activity. It differs from MET-ENKEPHALIN in the LEUCINE at position 5. Its first four amino acid sequence is identical to the tetrapeptide sequence at the N-terminal of BETA-ENDORPHIN.
A 21-amino acid peptide produced in a variety of tissues including endothelial and vascular smooth-muscle cells, neurons and astrocytes in the central nervous system, and endometrial cells. It acts as a modulator of vasomotor tone, cell proliferation, and hormone production. (N Eng J Med 1995;333(6):356-63)
Cell surface proteins that bind TACHYKININS with high affinity and trigger intracellular changes influencing the behavior of cells. Three classes of tachykinin receptors have been characterized, the NK-1; NK-2; and NK-3; which prefer, respectively, SUBSTANCE P; NEUROKININ A; and NEUROKININ B.
A neurotoxic isoxazole (similar to KAINIC ACID and MUSCIMOL) found in AMANITA mushrooms. It causes motor depression, ataxia, and changes in mood, perceptions and feelings, and is a potent excitatory amino acid agonist.
A potent natriuretic and vasodilatory peptide or mixture of different-sized low molecular weight PEPTIDES derived from a common precursor and secreted mainly by the HEART ATRIUM. All these peptides share a sequence of about 20 AMINO ACIDS.
Compounds that inhibit or block the activity of NEUROKININ-1 RECEPTORS.

Cardiovascular effects of nociceptin in unanesthetized mice. (1/118)

We evaluated the systemic hemodynamic effects induced by nociceptin (NC) and NC-related peptides, including the NC receptor antagonist [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2 ([F/G]NC(1-13)NH2) in unanesthetized normotensive Swiss Morini mice. Bolus intravenous injection of NC decreased mean blood pressure and heart rate. The hypotensive response to 10 nmol/kg NC lasted <10 minutes, whereas a more prolonged hypotension was evoked by 100 nmol/kg (from 114+/-3 to 97+/-2 mm Hg at 10 minutes, P<0.01). The latter dose reduced heart rate from 542+/-43 to 479+/-31 beats/min (P<0.05) and increased aortic blood flow by 41+/-5% (P<0.05). Hypotension and bradycardia were also evoked by NC(1-17)NH2 and NC(1-13)NH2 fragments, whereas NC(1-13)OH and NC(1-9)NH2 were ineffective. Thiorphan, an inhibitor of neutral endopeptidase 24.11, enhanced the hypotension induced by NC(1-13)NH2 and revealed the ability of NC(1-13)OH to decrease mean blood pressure. [F/G]NC(1-13)NH2, a recently synthesized antagonist of the NC receptor, did not alter basal mean blood pressure or heart rate, but it prevented the hypotension, bradycardia, and increase in aortic blood flow evoked by NC. In contrast, [F/G]NC(1-13)NH2 did not alter the hypotension induced by bradykinin or endomorphin-1 (a micro-receptor agonist), and the bradycardia induced by leu-enkephalin (a delta-receptor agonist) or U504885 (a synthetic kappa-receptor agonist). In conclusion, NC and some of its fragments cause hypotension and bradycardia and increase aortic blood flow in mice, with the NC(1-13) sequence being critical for these biological effects. Our results also demonstrate that the compound [F/G]NC(1-13)NH2 is a potent and selective antagonist of the NC receptor in vivo.  (+info)

Interaction between neutral endopeptidase and angiotensin converting enzyme inhibition in rats with myocardial infarction: effects on cardiac hypertrophy and angiotensin and bradykinin peptide levels. (2/118)

Combined inhibition of neutral endopeptidase 24.11 (NEP) and angiotensin converting enzyme (ACE) is a candidate therapy for hypertension and cardiac failure. Given that NEP and ACE metabolize angiotensin (Ang) and bradykinin (BK) peptides, we investigated the effects of NEP inhibition and combined NEP and ACE inhibition on Ang and BK levels in rats with myocardial infarction. We administered the NEP inhibitor ecadotril (0, 0.1, 1, 10, and 100 mg/kg/day), either alone or together with the ACE inhibitor perindopril (0.2 mg/kg/day) by 12-hourly gavage from day 2 to 28 after infarction. Ecadotril increased urine cyclic GMP and BK-(1-9) excretion. Perindopril potentiated the effect of ecadotril on urine cyclic GMP excretion. Neither perindopril nor ecadotril reduced cardiac hypertrophy when administered separately, whereas the combination of perindopril and 10 or 100 mg/kg/day ecadotril reduced heart weight/body weight ratio by 10%. Administration of ecadotril to perindopril-treated rats decreased plasma Ang-(1-7) levels, increased cardiac BK-(1-9) levels, and increased Ang II levels in plasma, kidney, aorta, and lung. These data demonstrate interactions between the effects of NEP and ACE inhibition on remodeling of the infarcted heart and on Ang and BK peptide levels. Whereas increased cardiac BK-(1-9) levels may contribute to the reduction of cardiac hypertrophy, the reduction in plasma Ang-(1-7) levels and increase in Ang II levels in plasma and tissues may compromise the therapeutic effects of combined NEP/ACE inhibition.  (+info)

Effect of prolonged administration of a urinary kinase inhibitor, ebelactone B on the development of deoxycorticosterone acetate-salt hypertension in rats. (3/118)

The effect of prolonged administration of a carboxypeptidase Y-like kininase inhibitor, ebelactone B (EB) (2-ethyl-3, 11-dihydroxy-4, 6, 8, 10, 12-pentamethyl-9-oxo-6-tetradecenoic 1, 3-lactone), on the development of deoxycorticosterone acetate (DOCA)-salt hypertension was tested. The systolic blood pressure (SBP) of non-treated 6-week-old Sprague-Dawley strain rats was gradually increased by DOCA-salt treatment from 137+/-2 mmHg (n=11) to 195+/-7 mmHg at 10 weeks of age. With daily oral administration of lisinopril (5 mg kg(-1), twice a day), which is an inhibitor of angiotensin converting enzyme, a major kininase in plasma, the development of hypertension was not suppressed. By contrast, administration of EB (5 mg kg(-1), twice a day), completely inhibited the development of hypertension (SBP: 146+/-1 mmHg, n=5, 10 weeks old). The reduced SBP at 10 weeks of age was equal to the SBP before any treatment (142+/-1 mmHg, n=5). Direct determination of mean blood pressure (MBP) in conscious, unrestrained rats confirmed that MBP elevation was completely inhibited by EB. Continuous subcutaneous infusion (5 mg kg(-1) day(-1)) of HOE140, a bradykinin B2 receptor antagonist, restored the elevation of SBP, which was suppressed by EB. The weights of left ventricle of DOCA-salt treated rats 10-weeks-old (0.36+/-0.02 g 100 g body weight(-1), n=11) was significantly reduced by EB (0.27+/-0.01, n=5), as were the sodium levels in serum, cerebrospinal fluid and erythrocyte. These findings suggested that EB is effective in preventing salt-related hypertension presumably by eliminating sodium retention.  (+info)

A three-dimensional construction of the active site (region 507-749) of human neutral endopeptidase (EC.3.4.24.11). (4/118)

A three-dimensional model of the 507-749 region of neutral endopeptidase-24.11 (NEP; E.C.3.4.24.11) was constructed integrating the results of secondary structure predictions and sequence homologies with the bacterial endopeptidase thermolysin. Additional data were extracted from the structure of two other metalloproteases, astacin and stromelysin. The resulting model accounts for the main biological properties of NEP and has been used to describe the environment close to the zinc atom defining the catalytic site. The analysis of several thiol inhibitors, complexed in the model active site, revealed the presence of a large hydrophobic pocket at the S1' subsite level. This is supported by the nature of the constitutive amino acids. The computed energies of bound inhibitors correspond with the relative affinities of the stereoisomers of benzofused macrocycle derivatives of thiorphan. The model could be used to facilitate the design of new NEP inhibitors, as illustrated in the paper.  (+info)

Interaction of mammalian neprilysin with binding protein and calnexin in Schizosaccharomyces pombe. (5/118)

Neutral endopeptidase (neprilysin or NEP, EC 3.4.24.11) is a zinc metallo-endopeptidase expressed in many eukaryotic cell types and displaying several important physiological roles. In the brain (and central nervous system), this enzyme is involved in the molecular mechanism of pain by its action in the degradation of enkephalin molecules. In the kidney, NEP is implicated in the degradation of regulatory factors involved in the control of arterial pressure, including atrial natriuretic peptide and bradykinin. In this study we assessed the potential of the fission yeast Schizosaccharomyces pombe to overproduce rabbit NEP and secreted NEP (sNEP, a soluble derivative of this integral membrane protein). Both recombinant NEP and sNEP were produced at high levels (5 mg/l) in this system. Enzymic studies revealed that these recombinant proteins were fully active and exhibit kinetic parameters similar to those of the bona fide enzyme. Immunofluorescence microscopy and enzymic assays demonstrated that recombinant NEP is correctly targeted to the cell membrane. Furthermore, co-immunoprecipitation studies showed that folding intermediates of NEP and sNEP, produced in S. pombe, interact in the endoplasmic reticulum (ER) with binding protein (BiP) and calnexin (Cnx1p). The amount of sNEP coprecipitated with both BiP and Cnx1p augmented when cells were subjected to various stresses causing the accumulation of unfolded proteins in the ER. The interactions of NEP with BiP and Cnx1p were, however, more refractive to the same stresses.  (+info)

The contribution of nitric oxide to diuretic and natriuretic effects of renal kinins in normotensive rats. (6/118)

We have reported that diuresis and natriuresis due to increase in renal kinins induced by the neutral endopeptidase 24.11 (NEP) inhibitor were attenuated by nitric oxide (NO) synthase inhibitor. To further clarify the water-sodium excretory mechanism of renal kinins, we estimated NO2+NO3 (NOx) and cGMP in plasma and urine with and without a specific NEP inhibitor, thiorphan. P-aminohippuric acid (PAH) and inulin were injected into male Sprague-Dawley rats. Vehicle (n = 8) or thiorphan (30 mg/kg, n = 10) was injected after the control period. Mean blood pressure (MBP), plasma and urinary PAH, inulin, NOx and cGMP, urinary volume (UV) and urinary sodium excretion (UNaV) were measured before and after injection of the reagents. MBP, renal plasma flow and glomerular filtration rate were not affected by thiorphan. Plasma NOx and cGMP with thiorphan did not differ from the vehicle, while urinary NOx and cGMP increased. None of the variables were affected by vehicle. UV and UNaV were higher with thiorphan than with vehicle. Positive correlation was found between urinary deltaNOx and deltacGMP. Each urinary deltaNOx and deltacGMP was significantly correlated to both deltaUV and deltaUNaV. Urinary NOx and cGMP were increased while maintaining correlations to UV and UNaV, but plasma NOx and cGMP were not affected by thiorphan. This implies that the mechanism of water-sodium excretion induced by NEP inhibitor is mediated by renal NO. Therefore, renal NO may contribute to the diuretic and natriuretic effects of renal kinins.  (+info)

Nitric oxide modulates mitochondrial respiration in failing human heart. (7/118)

Background-Our objective for this study was to investigate whether nitric oxide (NO) modulates tissue respiration in the failing human myocardium. Methods and Results-Left ventricular free wall and right ventricular tissue samples were taken from 14 failing explanted human hearts at the time of transplantation. Tissue oxygen consumption was measured with a Clark-type oxygen electrode in an airtight stirred bath containing Krebs solution buffered with HEPES at 37 degrees C (pH 7.4). Rate of decrease in oxygen concentration was expressed as a percentage of the baseline, and results of the highest dose are indicated. Bradykinin (10(-4) mol/L, -21+/-5%), amlodipine (10(-5) mol/L, -14+/-5%), the ACE inhibitor ramiprilat (10(-4) mol/L, -21+/-2%), and the neutral endopeptidase inhibitor thiorphan (10(-4) mol/L, -16+/-5%) all caused concentration-dependent decreases in tissue oxygen consumption. Responses to bradykinin (-2+/-6%), amlodipine (-2+/-4%), ramiprilat (-5+/-6%), and thiorphan (-4+/-7%) were significantly attenuated after NO synthase blockade with N-nitro-L-arginine methyl ester (10(-4) mol/L; all P<0.05). NO-releasing compounds S-nitroso-N-acetyl-penicillamine (10(-4) mol/L, -34+/-5%) and nitroglycerin (10(-4) mol/L, -21+/-5%), also decreased tissue oxygen consumption in a concentration-dependent manner. However, the reduction in tissue oxygen consumption in response to S-nitroso-N-acetyl-penicillamine (-35+/-7%) or nitroglycerin (-16+/-5%) was not significantly affected by N-nitro-L-arginine methyl ester. Conclusions-These results indicate that the modulation of oxygen consumption by both endogenous and exogenous NO is preserved in the failing human myocardium and that the inhibition of kinin degradation plays an important role in the regulation of mitochondrial respiration.  (+info)

Targeted deletion of the neutral endopeptidase gene alters ventilatory responses to acute hypoxia in mice. (8/118)

Neutral endopeptidase (NEP) is one of the major endopeptidases responsible for the inactivation of substance P in the carotid body, a neurotransmitter shown to be important in the transduction of hypoxic stimuli. Ventilatory responses to acute hypoxia were measured by indirect plethysmography in unanesthetized, unrestrained wild-type mice and in mice in which the NEP gene was deleted (NEP -/-). Ventilation was measured while the animals breathed room air: 12% O(2) in N(2) and 8% O(2) in N(2). Deletion of the NEP gene caused marked alterations in both the magnitude and composition of the hypoxic ventilatory response to both 8% O(2) in N(2) and 12% O(2) in N(2), compared with the wild-type mice (C57BL/6J) on the same genetic background as the NEP -/- mice. Treatment of C57BL/6J mice with thiorphan, a NEP inhibitor, resulted in a greater ventilatory response to 8% O(2) because of a significantly greater shortening of expiratory time. The results of these studies demonstrate that NEP plays an important role in modifying the expression of the ventilatory response to acute hypoxia.  (+info)

Thiorphan is not a medical condition or disease, but rather a synthetic medication. It is a potent inhibitor of membrane-bound metalloendopeptidases, also known as neprilysin enzymes. These enzymes are responsible for breaking down certain peptides in the body, including some hormones and neurotransmitters.

Thiorphan has been used in research to study the role of these enzymes in various physiological processes. It is also being investigated as a potential therapeutic agent for conditions such as hypertension, heart failure, and Alzheimer's disease. However, it is not currently approved for clinical use in humans.

Therefore, there is no medical definition of 'Thiorphan' as a condition or disease.

Neprilysin (NEP), also known as membrane metallo-endopeptidase or CD10, is a type II transmembrane glycoprotein that functions as a zinc-dependent metalloprotease. It is widely expressed in various tissues, including the kidney, brain, heart, and vasculature. Neprilysin plays a crucial role in the breakdown and regulation of several endogenous bioactive peptides, such as natriuretic peptides, bradykinin, substance P, and angiotensin II. By degrading these peptides, neprilysin helps maintain cardiovascular homeostasis, modulate inflammation, and regulate neurotransmission. In the context of heart failure, neprilysin inhibitors have been developed to increase natriuretic peptide levels, promoting diuresis and vasodilation, ultimately improving cardiac function.

Tiopronin is a medication that belongs to a class of drugs called mucolytic agents. It works by breaking down mucus in the respiratory tract, making it easier to cough up and clear the airways. Tiopronin is also known as tiopronin sodium or Thiola®.

In addition to its use as a mucolytic agent, tiopronin has been found to be effective in reducing the formation of cystine kidney stones in patients with a rare genetic disorder called cystinuria. It works by binding to cystine in the urine and preventing it from forming into crystals or stones.

Tiopronin is available as a tablet or oral solution and is typically taken several times a day, with dosing adjusted based on the patient's individual needs and response to treatment. Common side effects of tiopronin include stomach upset, loss of appetite, and rash.

Neurokinin A (NKA) is a neuropeptide belonging to the tachykinin family, which also includes substance P and neurokinin B. It is widely distributed in the central and peripheral nervous systems and plays a role in various physiological functions such as pain transmission, smooth muscle contraction, and immune response regulation. NKA exerts its effects by binding to neurokinin 1 (NK-1) receptors, although it has lower affinity for these receptors compared to substance P. It is involved in several pathological conditions, including inflammation, neurogenic pain, and neurodegenerative disorders.

Protease inhibitors are a class of antiviral drugs that are used to treat infections caused by retroviruses, such as the human immunodeficiency virus (HIV), which is responsible for causing AIDS. These drugs work by blocking the activity of protease enzymes, which are necessary for the replication and multiplication of the virus within infected cells.

Protease enzymes play a crucial role in the life cycle of retroviruses by cleaving viral polyproteins into functional units that are required for the assembly of new viral particles. By inhibiting the activity of these enzymes, protease inhibitors prevent the virus from replicating and spreading to other cells, thereby slowing down the progression of the infection.

Protease inhibitors are often used in combination with other antiretroviral drugs as part of highly active antiretroviral therapy (HAART) for the treatment of HIV/AIDS. Common examples of protease inhibitors include saquinavir, ritonavir, indinavir, and atazanavir. While these drugs have been successful in improving the outcomes of people living with HIV/AIDS, they can also cause side effects such as nausea, diarrhea, headaches, and lipodystrophy (changes in body fat distribution).

Glycopeptides are a class of antibiotics that are characterized by their complex chemical structure, which includes both peptide and carbohydrate components. These antibiotics are produced naturally by certain types of bacteria and are effective against a range of Gram-positive bacterial infections, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE).

The glycopeptide antibiotics work by binding to the bacterial cell wall precursor, preventing the cross-linking of peptidoglycan chains that is necessary for the formation of a strong and rigid cell wall. This leads to the death of the bacteria.

Examples of glycopeptides include vancomycin, teicoplanin, and dalbavancin. While these antibiotics have been used successfully for many years, their use is often limited due to concerns about the emergence of resistance and potential toxicity.

Enkephalins are naturally occurring opioid peptides in the body that bind to opiate receptors and help reduce pain and produce a sense of well-being. There are two major types of enkephalins: Leu-enkephalin and Met-enkephalin, which differ by only one amino acid at the N-terminus.

Methionine-enkephalin (Met-enkephalin) is a type of enkephalin that contains methionine as its N-terminal amino acid. Its chemical formula is Tyr-Gly-Gly-Phe-Met, and it is derived from the precursor protein proenkephalin. Met-enkephalin has a shorter half-life than Leu-enkephalin due to its susceptibility to enzymatic degradation by aminopeptidases.

Met-enkephalin plays an essential role in pain modulation, reward processing, and addiction. It is also involved in various physiological functions, including respiration, cardiovascular regulation, and gastrointestinal motility. Dysregulation of enkephalins has been implicated in several pathological conditions, such as chronic pain, drug addiction, and neurodegenerative disorders.

Neurokinin-2 (NK-2) receptors are a type of G protein-coupled receptor that binds to and is activated by the neuropeptide substance P, which is a member of the tachykinin family. These receptors are widely distributed in the central and peripheral nervous systems and play important roles in various physiological functions, including pain transmission, smooth muscle contraction, and neuroinflammation.

NK-2 receptors are involved in the development of hyperalgesia (an increased sensitivity to pain) and allodynia (pain caused by a stimulus that does not normally provoke pain). They have also been implicated in several pathological conditions, such as inflammatory bowel disease, asthma, and neurodegenerative disorders.

NK-2 receptor antagonists have been developed and investigated for their potential therapeutic use in the treatment of various pain disorders, gastrointestinal diseases, and other medical conditions.

Tachykinins are a group of neuropeptides that share a common carboxy-terminal sequence and bind to G protein-coupled receptors, called tachykinin receptors. They are widely distributed in the nervous system and play important roles as neurotransmitters or neuromodulators in various physiological functions, such as pain transmission, smooth muscle contraction, and inflammation. The most well-known tachykinins include substance P, neurokinin A, and neuropeptide K. They are involved in many pathological conditions, including chronic pain, neuroinflammation, and neurodegenerative diseases.

Substance P is an undecapeptide neurotransmitter and neuromodulator, belonging to the tachykinin family of peptides. It is widely distributed in the central and peripheral nervous systems and is primarily found in sensory neurons. Substance P plays a crucial role in pain transmission, inflammation, and various autonomic functions. It exerts its effects by binding to neurokinin 1 (NK-1) receptors, which are expressed on the surface of target cells. Apart from nociception and inflammation, Substance P is also involved in regulating emotional behaviors, smooth muscle contraction, and fluid balance.

Endothelin-3 (ET-3) is a member of the endothelin family, which are small peptides with potent vasoconstrictor properties. ET-3 is primarily produced by neurons in the central and peripheral nervous system, and it plays important roles in the development and regulation of various physiological functions, including cardiovascular function, neurotransmission, and cell proliferation.

ET-3 exerts its effects by binding to specific G protein-coupled receptors, known as endothelin A (ETA) and endothelin B (ETB) receptors. These receptors are widely distributed throughout the body, including in the cardiovascular, respiratory, gastrointestinal, and genitourinary systems.

In addition to its role as a potent vasoconstrictor, ET-3 has been implicated in various pathological conditions, such as hypertension, heart failure, pulmonary arterial hypertension, and cancer. In recent years, there has been growing interest in the potential therapeutic use of endothelin receptor antagonists to treat these conditions.

Enkephalins are naturally occurring opioid peptides in the body that bind to opiate receptors and help reduce pain and produce a sense of well-being. There are two major types of enkephalins: Met-enkephalin and Leu-enkephalin, which differ by only one amino acid at position 5 (Leucine or Methionine).

Leu-enkephalin, also known as YGGFL, is a type of enkephalin that contains the amino acids Tyrosine (Y), Glycine (G), Glycine (G), Phenylalanine (F), and Leucine (L) in its sequence. It is involved in pain regulation, mood, and other physiological processes.

Leu-enkephalin is synthesized from a larger precursor protein called proenkephalin and is stored in the secretory vesicles of neurons. When released into the synaptic cleft, Leu-enkephalin can bind to opioid receptors on neighboring cells, leading to various physiological responses.

Leu-enkephalin has a shorter half-life than Met-enkephalin due to its susceptibility to enzymatic degradation by peptidases. However, it still plays an essential role in modulating pain and other functions in the body.

Endothelin-1 is a small peptide (21 amino acids) and a potent vasoconstrictor, which means it narrows blood vessels. It is primarily produced by the endothelial cells that line the interior surface of blood vessels. Endothelin-1 plays a crucial role in regulating vascular tone, cell growth, and inflammation. Its dysregulation has been implicated in various cardiovascular diseases, such as hypertension and heart failure. It exerts its effects by binding to specific G protein-coupled receptors (ETA and ETB) on the surface of target cells.

Tachykinin receptors are a type of G protein-coupled receptor (GPCR) that bind and respond to tachykinins, which are neuropeptides involved in various physiological functions such as neurotransmission, smooth muscle contraction, vasodilation, and pain perception. There are three main subtypes of tachykinin receptors: NK1, NK2, and NK3.

NK1 receptors primarily bind substance P, a neuropeptide that plays a role in neurotransmission, inflammation, and pain signaling. NK2 receptors mainly bind neurokinin A (NKA) and are involved in smooth muscle contraction, particularly in the respiratory and gastrointestinal tracts. NK3 receptors primarily bind neurokinin B (NKB) and are found in the central nervous system, where they play a role in regulating body temperature, feeding behavior, and sexual function.

Tachykinin receptors have been implicated in various pathological conditions such as chronic pain, inflammation, asthma, and neurodegenerative disorders. As a result, tachykinin receptor antagonists are being developed as potential therapeutic agents for these conditions.

Ibotenic acid is a naturally occurring neurotoxin that can be found in certain species of mushrooms, including the Amanita muscaria and Amanita pantherina. It is a type of glutamate receptor agonist, which means it binds to and activates certain receptors in the brain called N-methyl-D-aspartate (NMDA) receptors.

Ibotenic acid has been used in scientific research as a tool for studying the brain and nervous system. It can cause excitotoxicity, which is a process of excessive stimulation of nerve cells leading to their damage or death. This property has been exploited in studies involving neurodegenerative disorders, where ibotenic acid is used to selectively destroy specific populations of neurons to understand the functional consequences and potential therapeutic interventions for these conditions.

However, it's important to note that ibotenic acid is not used as a treatment or therapy in humans due to its neurotoxic effects. It should only be handled and used by trained professionals in controlled laboratory settings for research purposes.

Atrial natriuretic factor (ANF), also known as atrial natriuretic peptide (ANP), is a hormone that is primarily produced and secreted by the atria of the heart in response to stretching of the cardiac muscle cells due to increased blood volume. ANF plays a crucial role in regulating body fluid homeostasis, blood pressure, and cardiovascular function.

The main physiological action of ANF is to promote sodium and water excretion by the kidneys, which helps lower blood volume and reduce blood pressure. ANF also relaxes vascular smooth muscle, dilates blood vessels, and inhibits the renin-angiotensin-aldosterone system (RAAS), further contributing to its blood pressure-lowering effects.

Defects in ANF production or action have been implicated in several cardiovascular disorders, including heart failure, hypertension, and kidney disease. Therefore, ANF and its analogs are being investigated as potential therapeutic agents for the treatment of these conditions.

Neurokinin-1 (NK-1) receptor antagonists are a class of drugs that block the action of substance P, a neuropeptide involved in pain transmission and inflammation. These drugs work by binding to NK-1 receptors found on nerve cells, preventing substance P from activating them and transmitting pain signals. NK-1 receptor antagonists have been studied for their potential use in treating various conditions associated with pain and inflammation, such as migraine headaches, depression, and irritable bowel syndrome. Some examples of NK-1 receptor antagonists include aprepitant, fosaprepitant, and rolapitant.

... is the active metabolite of the antidiarrheal racecadotril (acetorphan). It prevents the degradation of endogenous ...
... thiorphan Racecadotril (acetorphan) - racemic form of dexecadotril and ecadotril; prodrug to thiorphan Sacubitril - prodrug to ... thiorphan Ecadotril (sinorphan) - (S)-enantiomer of racecadotril; prodrug to (S)- ... sacubitrilat Sacubitrilat - active metabolite of sacubitril Thiorphan - active metabolite of racecadotril UK-414,495 Non- ...
S. L. Roderick; M. C. Fournie-Zaluski; B. P. Roques; B. W. Matthews (February 1989). "Thiorphan and retro-thiorphan display ... Thermolysin complexed with the inhibitor (S)-thiorphan are isomeric thiol-containing inhibitors of endopeptidase EC 24-11 (also ...
Thiorphan is further metabolized to inactive metabolites such as the methyl thioether and the methyl sulfoxide. Both active and ... Thiorphan is the active metabolite of racecadotril, which exerts the bulk of its inhibitory actions on enkephalinases. ... The active metabolite of racecadotril, thiorphan, inhibits enkephalinase enzymes in the intestinal epithelium with an IC50 of ... is rapidly and effectively metabolized to the moderately active S-acetylthiorphan the main active metabolite thiorphan, of ...
2000). "Thiorphan, an inhibitor of neutral endopeptidase/enkephalinase (CD10/CALLA) enhances cell proliferation in bone marrow ...
Benzylmercapturic acid Thiorphan This set index page lists chemical structure articles associated with the same molecular ...
... thiorphan MeSH D12.125.190.055 - aminoisobutyric acids MeSH D12.125.190.350 - gamma-aminobutyric acid MeSH D12.125.190.350.900 ... thiorphan MeSH D12.125.740.025 - 2-amino-5-phosphonovalerate MeSH D12.125.740.675 - phosphocreatine MeSH D12.125.740.700 - ...
... thiorphan MeSH D02.886.092.408 - endosulfan MeSH D02.886.250.050 - 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid ...
The enkephalinase inhibitor thiorphan shows antinociceptive activity in mice », Nature, 1980, 288, p. 286-288 Roge J, Baumer P ...
Thiorphan is the active metabolite of the antidiarrheal racecadotril (acetorphan). It prevents the degradation of endogenous ...
The potencies of the R and S isomers of thiorphan and rigid analogs of thiorphan to produce analgesia in a mouse hot-plate ... Thiorphan and analogs: lack of correlation between potency to inhibit "enkephalinase A" in vitro and analgesic potency in vivo ... D L 3-Mercapto-2-Benzylpropanoyl-Glycine (Thiorphan). Price. 5 mg ,$85. Sequence: D L 3-Mercapto-2-Benzylpropanoyl-Glycine. M.W ... Thiorphan - N-(3-mercapto-2-benzylpropanoyl)-glycine:. H.P.Rang`s "Pharmacology" says:. Enkephallinase inhibitors, such as ...
... thiorphan; verapamil; and TMB8. The constrictor effects of the dust extracts were inhibited by a wide variety of agents, the ...
Thiorphan. Sigma Aldrich. Cat# T6031. Chemical compound, drug. MPEP. R and D Systems/Tocris. Cat# 1212. ...
The stock solutions for all drugs, except thiorphan, were made in Milli-Q water. Thiorphan was dissolved in DMSO to achieve a ... 2D,E, see thiorphan bars in E). This suggests that the ability of neprilysin to protect met-enk from degradation is enhanced ... E, Bar chart showing the proportion of met-enk inhibition prevented by the activity of neprilysin alone (thiorphan bars), or by ... thiorphan alone, control vs withdrawal, t(18) = 2.87, p = 0.01; PI cocktail, control vs withdrawal, t(8) = 2.61, p = 0.03). F, ...
Higher doses of thiorphan did not exert such effects, possibly because NEPi-induced ET-1 accumulation now counteracted its ... TGR(mREN2)27 rats were treated for three weeks with vehicle, the ARB irbesartan (IRB) or IRB + the NEPi thiorphan (0.1 and 1.0 ...
2H7]-D,L-Thiorphan. Product Number: C5552 CAS number: 76721-89-6 unlabeled ...
Thiorphan/*analogs & derivatives Neprilysin/antagonists & inhibitors. J Biol Chem 1992 Feb 5;267(4):2138-41 SCH 42495 136511-43 ... Thiorphan/*analogs & derivatives Neprilysin/antagonists & inhibitors. Pharma Action Antidiarrheals ; Protease Inhibitors J ... The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to ...
263 136 135 similarity 229 RESP method 143 retro-thiorphan 235, 236, 237 RIA, cAMP binding region rigid analogs 226 147, 150 ...
Thiorphan-d5. *Rosiglitazone-d3. *Ritonavir-d6. *Ritonavir-13C-D3. *Raltegravir-d3 Potassium ...
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... of maximal with thiorphan. Coexpression of NEP in the same cells as the SPR also reduced to undetectable the increase in ... of maximal with thiorphan. Coexpression of NEP in the same cells as the SPR also reduced to undetectable the increase in ... of maximal with thiorphan. Coexpression of NEP in the same cells as the SPR also reduced to undetectable the increase in ... of maximal with thiorphan. Coexpression of NEP in the same cells as the SPR also reduced to undetectable the increase in ...
During suffusion with bradykinin (1.0 μM) and thiorphan, the number of leaky sites increased significantly from 15±3 to 47±7 ... The selective, active site-directed neutral endopeptidase inhibitors phosphoramidon (1.0 μM) and thiorphan (10.0 μM) and the ... The selective, active site-directed neutral endopeptidase inhibitors phosphoramidon (1.0 μM) and thiorphan (10.0 μM) and the ... The selective, active site-directed neutral endopeptidase inhibitors phosphoramidon (1.0 μM) and thiorphan (10.0 μM) and the ...
... thiorphan and neostigmine (inhibitors of enkephalinase and acetylcholinesterase, resp.), gabapentin (a GABA releaser), and ...
... and thiorphan (D, L, 3-mercapto-2-benzylpropanoyl-glycine). [0118]Fibronectin peptides including, but not limited to platelet ...
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Once Loo Chek Suspension is inside your body it is broken down into an active ingredient called thiorphan. Thiorphan works by ...
Thiorphan is further metabolized to inactive metabolites such as the methyl thioether and the methyl sulfoxide. Legislation has ...
44 as well as thiorphan. Nonetheless, the particular management of an try out 44 as well as thiorphan ended in an important ... rhesus apes through intracranial treatment of the experiment with 42 along with thiorphan, a great chemical of neprilysin ...
Thiorphan and phosphoramidon, two particular inhibitors of the group of endopeptidases, had been utilized to determine that ...
... and the enkephalinase inhibitor thiorphan (0.1-1 μg) were ineffective. damgo (0.1-10 ng) increased social play after infusion ...
Neprilysin degrades both amyloid β peptide 1-40 and 1-42 most effectively among thiorphan- and phosphoramidon-sensitive ...
Captopril-Sensitive Peptidyl Dipeptidase A and Thiorphan-Sensitive Endopeptidase-24.11 in Mouse Vas Deferens. The Japanese ...
... thiorphan, phosphoramidon), mixed NEP and ACE inhibitors (omapatrilat), guanylin and uroguanylin, kinins, prostaglandins of the ...
Sulodictil and DL-Thiorphan were dissolved in DMSO to a concentration of 50 g/L. seven Viability assays Cell viability was ...
AD 10 Sachet 1 gm is a pro-drug which breaks down into thiorphan (the active form) and works by decreasing the amount of salts ...
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