Nylidrin
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Identification
- Summary
Nylidrin is a vasodilator used to treat patients with peripheral vascular disorders, and elderly patients with symptoms associated with organic mental disorders.
- Generic Name
- Nylidrin
- DrugBank Accession Number
- DB06152
- Background
Nylidrin, also known as buphenine belongs to the category of drugs called vasodilators, which relax blood vessels and increase blood flow. Nylidrin is a peripheral vasodilator. Some studies show the evidence of improving cognitive impairment in selected individuals, such as geriatric patients with mild to moderate symptoms of cognitive, emotional and physical impairment 4.
Nylidrin is utilized to treat several disorders that may benefit from increased blood flow (for example, certain mental disorders, blood vessel disease due to diabetes, frostbite, night leg cramps, and certain types of ulcers). This medication works by dilating (widening) blood vessels to help increase blood flow (improving circulation) throughout the body, including the extremities and central nervous system. This effect may help to improve memory/judgment, improve walking ability, and support the healing of frostbite/ulcers 6.
FDA has considered nylidrin as "lacking substantial evidence of effectiveness" in cerebral ischemia, cerebral arteriosclerosis, and other cerebral circulatory insufficiencies. Therefore, the FDA has withdrawn nylidrin from the U.S. market 9.
- Type
- Small Molecule
- Groups
- Approved
- Structure
- Weight
- Average: 299.414
Monoisotopic: 299.188529049 - Chemical Formula
- C19H25NO2
- Synonyms
- Bufenina
- Buphenin
- Buphenine
- Bupheninum
- External IDs
- CS 6712
- SKF 1700-A
Pharmacology
- Indication
Nylidrin is mainly indicated in conditions like arteriosclerosis, cerebrovascular disease, peripheral vascular disease, Raynaud's disease, thrombo-angitis obliterans, and thrombophlebitis 8. It may sometimes be used in the treatment of peripheral vascular disorders in addition premature labor (however, the drug is not approved for premature labor)2.
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- Pharmacodynamics
Nylidrin hydrochloride acts mainly by beta-receptor stimulation 1, 15. Beta stimulation with nylidrin has been studied and confirmed in a variety of isolated tissues from rabbits, guinea pigs, as well as dogs. This drug has been shown to dilate arterioles in skeletal muscle and to increase cardiac output in the anesthetized dog and cat as well as the unanesthetized man. An increase in cerebral blood flow and a decrease in vascular resistance has also been reported. The result of this combination of mechanisms is an improved blood supply to ischemic tissues, with minimal change in blood pressure (generally) 16.
Nylidrin causes peripheral vasodilation, a positive inotropic effect, and an increased volume of gastric acid. 2, 4. According to one study, there are two primary effects of this agent following the intra‐arterial route of administration: one, to decrease total peripheral resistance; and two, a direct effect on the heart tissue to increase cardiac output 15. It also acts directly on the arteries and arterioles of the skeletal muscles. Additionally, it suppresses uterine contractility thereby preventing or halting premature labor 11.
- Mechanism of action
This drug is classified as a beta receptor agonist 7.The β2-adrenergic receptor belongs to the widely expressed 7-transmembrane receptors superfamily, which signals through heterotrimeric G-proteins. They are frequently referred to as G-protein-coupled receptors because they accomplish signal transduction to the interior of the cell by interactions with guanine nucleotide regulatory binding proteins. The receptor-coupled G-proteins work as “molecular switches” which alternate from an inactive guanosine-diphosphate to an active guanosine-triphosphate (GTP) state, which then act to modulate all downstream cell processes. Signaling by various hormones and neurotransmitters, as well as photons and odors, follows the same general pathway, (i.e., by binding of an extracellular ligand to the receptor, which then interacts with the membrane-bound G-protein). This complex, often referred to as the ternary complex, then acts through the activated G-protein to regulate an effector, such as adenylyl cyclase, phospholipase C, or ion channels 14.
The main effects of Nylidrin may be divided into 3 categories:
Blood vessels
Vascular smooth muscle has β2-adrenoceptors that have a high binding affinity for circulating epinephrine and a lower affinity to norepinephrine released by sympathetic adrenergic nerves 16. When nylidrin binds to the beta-adrenergic receptors, it prevents the binding of epinephrine, leading to decreased blood vessel contractility as epinephrine is unable to bind 18.
Heart:
Increased intracellular cAMP by beta-2-agonists inhibits myosin light chain kinase, leading to relaxation These receptors, like the receptors in the heart, are coupled to a Gs-protein, which acts stimulate the formation of cAMP. Although increased cAMP increases cardiac myocyte contraction, in vascular smooth muscle, an increase in cAMP causes smooth muscle relaxation. The reason for this is the fact that cAMP inhibits myosin light chain kinase that is responsible for phosphorylating smooth muscle myosin. Increases in intracellular cAMP caused by β2-agonists inhibit myosin light chain kinase thereby producing less contractile force (i.e., promoting relaxation) 16.
Other tissues
Activation of β2-adrenoceptors in the lungs causes bronchodilation. β2-adrenoceptor activation leads to hepatic glycogenolysis and the pancreatic secretion of glucagon, increasing plasma glucose concentrations. β1-adrenoceptor stimulation in the kidneys promotes the release of renin, stimulating the production of angiotensin II and the subsequent release of aldosterone by the adrenal cortex 16.
Target Actions Organism AInterferon alpha/beta receptor 2 agonistHumans UVoltage-dependent T-type calcium channel subunit alpha-1I antagonistagonistHumans - Absorption
Readily absorbed from the gastrointestinal tract 4.
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Duration of action is 10h 9.
- Clearance
Not Available
- Adverse Effects
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- Toxicity
Adverse effects of oral sympathomimetics, such as Nylidrin, are common. The most frequent effects are hypertension, palpitations, nausea, anxiety, mydriasis, and restlessness/agitation 9.
Large overdoses and severe toxicity may lead to seizures, hallucinations, agitated delirium, and tachydysrhythmias including supraventricular tachycardia and ventricular tachycardia. Vasospasm can lead to myocardial ischemia focal cerebrovascular deficits. Severe hypertension may also result in intracranial hemorrhage or renal insufficiency. Reflex bradycardia because of significant hypertension is possible. Prolonged agitation can lead to rhabdomyolysis and hyperthermia 9.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Nylidrin can be increased when it is combined with Abametapir. Acarbose The risk or severity of hypoglycemia can be increased when Nylidrin is combined with Acarbose. Acebutolol Acebutolol may increase the arrhythmogenic activities of Nylidrin. Aceclofenac The risk or severity of hypertension can be increased when Nylidrin is combined with Aceclofenac. Acemetacin The risk or severity of hypertension can be increased when Nylidrin is combined with Acemetacin. - Food Interactions
- Take with or without food. The absorption is unaffected by food.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Nylidrin hydrochloride EC69E3PW7E 849-55-8 CLJHABUMMDMAFA-UHFFFAOYSA-N - International/Other Brands
- Arbid / Arlidin
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Arlidin Tablet 6 mg Oral Searchlight Pharma Inc 1955-12-31 2024-07-18 Canada Arlidin Forte Tab 12mg Tablet 12 mg Oral Aventis Pharma Ltd. 1974-12-31 2003-07-22 Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image PMS-nylidrin Tab 6mg Tablet 6 mg Oral Pharmascience Inc 1983-12-31 2016-10-28 Canada
Categories
- ATC Codes
- C04AA02 — Buphenine
- C04AA — 2-amino-1-phenylethanol derivatives
- C04A — PERIPHERAL VASODILATORS
- C04 — PERIPHERAL VASODILATORS
- C — CARDIOVASCULAR SYSTEM
- Drug Categories
- 2-Amino-1-Phenylethanol Derivatives
- Adrenergic Agents
- Adrenergic Agonists
- Adrenergic beta-Agonists
- Agents causing hyperkalemia
- Agents producing tachycardia
- Agents that produce hypertension
- Alcohols
- Amines
- Amino Alcohols
- Antiarrhythmic agents
- Autonomic Agents
- Bradycardia-Causing Agents
- Calcium Channel Blockers
- Cardiovascular Agents
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Ethylamines
- Genito Urinary System and Sex Hormones
- Miscellaneous Vasodilatating Agents
- Neurotransmitter Agents
- Peripheral Nervous System Agents
- Peripheral Vasodilators
- Phenethylamines
- Propanolamines
- Propanols
- Reproductive Control Agents
- Sympathomimetics
- Sympathomimetics, Labour Repressants
- Tocolytic Agents
- Vasodilating Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylpropanes. These are organic compounds containing a phenylpropane moiety.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Phenylpropanes
- Direct Parent
- Phenylpropanes
- Alternative Parents
- Aralkylamines / 1-hydroxy-2-unsubstituted benzenoids / Secondary alcohols / 1,2-aminoalcohols / Dialkylamines / Organopnictogen compounds / Hydrocarbon derivatives / Aromatic alcohols
- Substituents
- 1,2-aminoalcohol / 1-hydroxy-2-unsubstituted benzenoid / Alcohol / Amine / Aralkylamine / Aromatic alcohol / Aromatic homomonocyclic compound / Hydrocarbon derivative / Organic nitrogen compound / Organic oxygen compound
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 695DKH33EI
- CAS number
- 447-41-6
- InChI Key
- PTGXAUBQBSGPKF-UHFFFAOYSA-N
- InChI
- InChI=1S/C19H25NO2/c1-14(8-9-16-6-4-3-5-7-16)20-15(2)19(22)17-10-12-18(21)13-11-17/h3-7,10-15,19-22H,8-9H2,1-2H3
- IUPAC Name
- 4-{1-hydroxy-2-[(4-phenylbutan-2-yl)amino]propyl}phenol
- SMILES
- CC(CCC1=CC=CC=C1)NC(C)C(O)C1=CC=C(O)C=C1
References
- General References
- Niemeyer G, Cottier D, Resch H: Effects of buphenine (nylidrin) on the perfused mammalian eye. Graefes Arch Clin Exp Ophthalmol. 1987;225(1):33-8. [Article]
- Castren O, Gummerus M, Saarikoski S: Treatment of imminent premature labour. Acta Obstet Gynecol Scand. 1975;54(2):95-100. [Article]
- Walter U, Waldmann R, Nieberding M: Intracellular mechanism of action of vasodilators. Eur Heart J. 1988 Jun;9 Suppl H:1-6. [Article]
- PubChem, Nylidrin [Link]
- Nylidrin (Oral) [Link]
- Nylidrin - Oral [Link]
- Nylidrin [Link]
- Drug monograph [Link]
- ToxNet Nylidrin [Link]
- Central cardiovascular effects of nylidrin (buphenine) [Link]
- Buphenine, MIMS [Link]
- Central cardiovascular effects of nylidrin (buphenine). [Link]
- Nylidrin [Link]
- Beta-Adrenergic Agonists [Link]
- Local and systemic hemodynamic effects of nylidrin [Link]
- Nylidrin Hydrochloride [Link]
- Specific blockade of spasmogens by β‐receptor stimulation with nylidrin and isoprenaline [Link]
- NyIidrin HCL: A BETA-SYMPATHETIC STIMULANT IN THE MANAGEMENT OF HAEMORRHAGIC SHOCK [Link]
- External Links
- MSDS
- Download (107 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 12 mg Solution Oral Tablet Oral 6 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 217 MSDS - Predicted Properties
Property Value Source Water Solubility 0.0204 mg/mL ALOGPS logP 2.73 ALOGPS logP 3.05 Chemaxon logS -4.2 ALOGPS pKa (Strongest Acidic) 9.25 Chemaxon pKa (Strongest Basic) 10.11 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 52.49 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 90.06 m3·mol-1 Chemaxon Polarizability 34.56 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-001i-0492000000-b4b4e8b968a55b5b3c58 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-002b-3790000000-3efee9e35ed6cbaf1e69 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0059-1920000000-db1fc6e05980814de99f Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-008i-3910000000-f09e171347def8321b56 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-00dl-9730000000-e17c08c038c2a0b7c65a Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-7920000000-9d643f27b9e613b21525 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 172.63731 predictedDeepCCS 1.0 (2019) [M+H]+ 174.99532 predictedDeepCCS 1.0 (2019) [M+Na]+ 181.08847 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Together with IFNAR1, forms the heterodimeric receptor for type I interferons (including interferons alpha, beta, epsilon, omega and kappa) (PubMed:10049744, PubMed:10556041, PubMed:21854986, PubMed:26424569, PubMed:28165510, PubMed:32972995, PubMed:7665574, PubMed:7759950, PubMed:8181059, PubMed:8798579, PubMed:8969169). Type I interferon binding activates the JAK-STAT signaling cascade, resulting in transcriptional activation or repression of interferon-regulated genes that encode the effectors of the interferon response (PubMed:10049744, PubMed:17517919, PubMed:21854986, PubMed:26424569, PubMed:28165510, PubMed:32972995, PubMed:7665574, PubMed:7759950, PubMed:8181059, PubMed:8798579, PubMed:8969169). Mechanistically, type I interferon-binding brings the IFNAR1 and IFNAR2 subunits into close proximity with one another, driving their associated Janus kinases (JAKs) (TYK2 bound to IFNAR1 and JAK1 bound to IFNAR2) to cross-phosphorylate one another (PubMed:10556041, PubMed:11682488, PubMed:12105218, PubMed:21854986, PubMed:32972995). The activated kinases phosphorylate specific tyrosine residues on the intracellular domains of IFNAR1 and IFNAR2, forming docking sites for the STAT transcription factors (STAT1, STAT2 and STAT) (PubMed:11682488, PubMed:12105218, PubMed:21854986, PubMed:32972995). STAT proteins are then phosphorylated by the JAKs, promoting their translocation into the nucleus to regulate expression of interferon-regulated genes (PubMed:12105218, PubMed:28165510, PubMed:9121453)
- Specific Function
- cytokine binding
- Gene Name
- IFNAR2
- Uniprot ID
- P48551
- Uniprot Name
- Interferon alpha/beta receptor 2
- Molecular Weight
- 57758.24 Da
References
- ToxNet Nylidrin [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- AntagonistAgonist
- General Function
- Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. This channel gives rise to T-type calcium currents. T-type calcium channels belong to the 'low-voltage activated (LVA)' group and are strongly blocked by nickel and mibefradil. A particularity of this type of channels is an opening at quite negative potentials, and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes. Gates in voltage ranges similar to, but higher than alpha 1G or alpha 1H (By similarity)
- Specific Function
- high voltage-gated calcium channel activity
- Gene Name
- CACNA1I
- Uniprot ID
- Q9P0X4
- Uniprot Name
- Voltage-dependent T-type calcium channel subunit alpha-1I
- Molecular Weight
- 245100.8 Da
References
- Central cardiovascular effects of nylidrin (buphenine). [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol
- Specific Function
- catechol O-methyltransferase activity
- Gene Name
- COMT
- Uniprot ID
- P21964
- Uniprot Name
- Catechol O-methyltransferase
- Molecular Weight
- 30036.77 Da
References
- Kurki T, Schultz E, Linden IB, Ylikorkala O: Catechol-O-methyltransferase activity in red blood cells in threatened preterm labor; effect of indomethacin and nylidrin. Acta Obstet Gynecol Scand. 1991;70(3):187-91. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Uesawa Y, Takeuchi T, Mohri K: Integrated analysis on the physicochemical properties of dihydropyridine calcium channel blockers in grapefruit juice interactions. Curr Pharm Biotechnol. 2012 Jul;13(9):1705-17. [Article]
Drug created at January 21, 2008 02:19 / Updated at October 29, 2024 18:21