Identification

Name
Nylidrin
Accession Number
DB06152
Type
Small Molecule
Groups
Approved
Description

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 Therefore, the FDA has withdrawn nylidrin from the U.S. market [9].

Structure
Thumb
Synonyms
  • Bufenina
  • Buphenin
  • Buphenine
  • Bupheninum
External IDs
CS 6712 / SKF 1700-A
Product Ingredients
IngredientUNIICASInChI Key
Nylidrin hydrochlorideEC69E3PW7E849-55-8CLJHABUMMDMAFA-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Arlidin Forte Tab 12mgTablet12 mgOralAventis Pharma Ltd.1974-12-312003-07-22Canada
Arlidin Tablets 6mgTablet6 mgOralErfa Canada 2012 Inc1955-12-31Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PMS-nylidrin Tab 6mgTablet6 mgOralPharmascience Inc1983-12-312016-10-28Canada
International/Other Brands
Arbid / Arlidin
Categories
UNII
695DKH33EI
CAS number
447-41-6
Weight
Average: 299.414
Monoisotopic: 299.188529049
Chemical Formula
C19H25NO2
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

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].

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].

TargetActionsOrganism
UVoltage-dependent T-type calcium channel subunit alpha-1I
antagonist
agonist
Human
AInterferon alpha/beta receptor 2
agonist
Human
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
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].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of adverse effects can be increased when Nylidrin is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Nylidrin is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe risk or severity of adverse effects can be increased when Nylidrin is combined with 3-isobutyl-1-methyl-7H-xanthine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Nylidrin is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Nylidrin is combined with 4-Bromo-2,5-dimethoxyamphetamine.
6-O-benzylguanineThe risk or severity of adverse effects can be increased when Nylidrin is combined with 6-O-benzylguanine.
7-DeazaguanineThe risk or severity of adverse effects can be increased when Nylidrin is combined with 7-Deazaguanine.
7,9-DimethylguanineThe risk or severity of adverse effects can be increased when Nylidrin is combined with 7,9-Dimethylguanine.
8-azaguanineThe risk or severity of adverse effects can be increased when Nylidrin is combined with 8-azaguanine.
8-chlorotheophyllineThe risk or severity of adverse effects can be increased when Nylidrin is combined with 8-chlorotheophylline.
Food Interactions
  • Take without regard to meals.

References

General References
  1. 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. [PubMed:2883089]
  2. Castren O, Gummerus M, Saarikoski S: Treatment of imminent premature labour. Acta Obstet Gynecol Scand. 1975;54(2):95-100. [PubMed:1094787]
  3. Walter U, Waldmann R, Nieberding M: Intracellular mechanism of action of vasodilators. Eur Heart J. 1988 Jun;9 Suppl H:1-6. [PubMed:3049092]
  4. PubChem, Nylidrin [Link]
  5. Nylidrin (Oral) [Link]
  6. Nylidrin - Oral [Link]
  7. Nylidrin [Link]
  8. Drug monograph [Link]
  9. ToxNet Nylidrin [Link]
  10. Central cardiovascular effects of nylidrin (buphenine) [Link]
  11. Buphenine, MIMS [Link]
  12. Central cardiovascular effects of nylidrin (buphenine). [Link]
  13. Nylidrin [Link]
  14. Beta-Adrenergic Agonists [Link]
  15. Local and systemic hemodynamic effects of nylidrin [Link]
  16. Nylidrin Hydrochloride [Link]
  17. Specific blockade of spasmogens by β‐receptor stimulation with nylidrin and isoprenaline [Link]
  18. NyIidrin HCL: A BETA-SYMPATHETIC STIMULANT IN THE MANAGEMENT OF HAEMORRHAGIC SHOCK [Link]
External Links
PubChem Compound
4567
PubChem Substance
347827757
ChemSpider
4407
ChEBI
91656
ChEMBL
CHEMBL114655
Wikipedia
Nylidrin
ATC Codes
G02CA02 — BuphenineC04AA02 — Buphenine
AHFS Codes
  • 24:12.92 — Miscellaneous Vasodilatating Agents
MSDS
Download (107 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral12 mg
TabletOral6 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)217MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.0204 mg/mLALOGPS
logP2.73ALOGPS
logP3.05ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)9.25ChemAxon
pKa (Strongest Basic)10.11ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area52.49 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity90.06 m3·mol-1ChemAxon
Polarizability34.56 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Phenylpropane / 1-hydroxy-2-unsubstituted benzenoid / Phenol / Aralkylamine / 1,2-aminoalcohol / Secondary alcohol / Secondary aliphatic amine / Secondary amine / Hydrocarbon derivative / Organopnictogen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
Agonist
General Function
Voltage-gated calcium channel activity
Specific 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, hor...
Gene Name
CACNA1I
Uniprot ID
Q9P0X4
Uniprot Name
Voltage-dependent T-type calcium channel subunit alpha-1I
Molecular Weight
245100.8 Da
References
  1. Central cardiovascular effects of nylidrin (buphenine). [Link]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Type i interferon receptor activity
Specific Function
Associates with IFNAR1 to form the type I interferon receptor. Receptor for interferons alpha and beta. Involved in IFN-mediated STAT1, STAT2 and STAT3 activation. Isoform 1 and isoform 2 are direc...
Gene Name
IFNAR2
Uniprot ID
P48551
Uniprot Name
Interferon alpha/beta receptor 2
Molecular Weight
57758.24 Da
References
  1. ToxNet Nylidrin [Link]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
O-methyltransferase activity
Specific 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-DOP...
Gene Name
COMT
Uniprot ID
P21964
Uniprot Name
Catechol O-methyltransferase
Molecular Weight
30036.77 Da
References
  1. 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. [PubMed:1927294]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. 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. [PubMed:22039822]

Drug created on January 20, 2008 19:19 / Updated on October 16, 2018 08:38