Nylidrin

299.4073

299.41

207-182-2

695DKH33EI

DTXSID4023387

Crystals from methanol

C - Cardiovascular system|G - Genito urinary system and sex hormones

52.5

3.3 (est)

White Powder

1.101 g/cm3

111-112 °C

476ºC at 760 mmHg

127.3ºC

1.579

In water, 1.1X10+3 mg/L at 25 deg C (est)

Store below 40 deg C (104 deg. F), preferably between 15 and 30 deg C (59 and 86 deg F), unless otherwise specified by manufacturer. Store in a tight container.

4.1X10-9 mm Hg at 25 deg C (est)

ODORLESS

TASTELESS

BETWEEN 4.5 & 6.5 (1% SOLN)

Henry's Law constant = 1.7X10-15 atm-cu m/mol at 25 °C (est)

pKa = 9.4 (secondary amine) (est)

WHITE CRYSTALLINE POWDER /HYDROCHLORIDE/|White crystals or powder, odorless; tasteless. pH of 1% solution is between 4.5 and 6.5 /Hydrochloride/|Hydroxyl radical reaction rate constant = 1.6X10-10 cu cm/molecule-sec at 25 °C (est)

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Adverse effects of oral sympathomimetics, such as Nylidrin, are common. The most frequent effects are hypertension, palpitations, nausea, anxiety, mydriasis, and restlessness/agitation. 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.

EFFECTS OF ANTIHISTAMINES WITH PHENOTHIAZINE STRUCTURE ARE ENHANCED BY NYLIDRIN BY DISPLACEMENT OF PHENOTHIAZINE FROM RECEPTOR SITES & TISSUES & BY CEREBRAL VASODILATOR EFFECT OF NYLIDRIN. ALTHOUGH CLINICAL DOCUMENTATION IS LACKING, PHENOTHIAZINE ACTIVITY MAY BE ENHANCED BY CONCURRENT USE OF NYLIDRIN.|PRETREATMENT OF RATS WITH NYLIDRIN PROTECTED AGAINST ACUTE TOXICITY OF SODIUM CYANIDE.

Nylidrin is mainly indicated in conditions like arteriosclerosis, cerebrovascular disease, peripheral vascular disease, Raynaud's disease, thrombo-angitis obliterans, and thrombophlebitis. 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).

Mesh Heading: adrenergic beta-Agonists, sympathomimetics, tocolytic Agents, vasodilator Agents|Nylidrin is considered only "possibly" effective for its labeled indication, which includes peripheral vasospastic disorders such as arteriosclerosis obliterans; thromboangiitis obliterans; diabetic vascular disease; night leg cramps; Raynaud's phenomenon and disease; frostbite; acrocyanosis; acroparesthesia; thrombophlebitis; and cold feet, legs, and hands.|FDA has classified nylidrin as "lacking substantial evidence of effectiveness" in cerebral ischemia, cerebral arteriosclerosis, and other circulatory insufficiencies of the brain. Therefore, the FDA has withdrawn nylidrin from the U.S. market.|.../IT/ IS USED IN TREATMENT OF VASCULAR DISORDERS OF EXTREMITIES THAT MAY INVOLVE SKELETAL MUSCLE VESSELS, SUCH AS INTERMITTENT CLAUDICATION, THROMBOPHLEBITIS & TO LESSER EXTENT, DIABETIC VASCULAR DISEASE. ...IT IS EFFECTIVE ONLY TO EXTENT THAT THERE MAY BE VASOSPASTIC COMPONENT IN THESE DISORDERS...|For more Therapeutic Uses (Complete) data for NYLIDRIN (11 total), please visit the HSDB record page.

.../IT/ SHOULD NOT BE USED IN PT WITH ANGINA PECTORIS OR WITH RECENT OR OLD MYOCARDIAL INFARCTIONS.|Heavy smoking may interfere with the therapeutic effect of nylidrin because nicotine constricts blood vessels.|Appropriate studies on the relationship of age to the effects of nylidrin have not been performed in the geriatric population. However, the risk of nylidrin-induced hypothermia may be increased in elderly patients.|SHOULD BE USED WITH CAUTION IN PT WITH MYOCARDIAL LESIONS, THYROTOXICOSIS, OR SEVERE ANGINA PECTORIS.|For more Drug Warnings (Complete) data for NYLIDRIN (6 total), please visit the HSDB record page.

Nylidrin hydrochloride acts mainly by beta-receptor stimulation,. 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). Nylidrin causes peripheral vasodilation, a positive inotropic effect, and an increased volume of gastric acid.,. 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. It also acts directly on the arteries and arterioles of the skeletal muscles. Additionally, it suppresses uterine contractility thereby preventing or halting premature labor.

Drugs that prevent preterm labor and immature birth by suppressing uterine contractions (TOCOLYSIS). Agents used to delay premature uterine activity include magnesium sulfate, beta-mimetics, oxytocin antagonists, calcium channel inhibitors, and adrenergic beta-receptor agonists. The use of intravenous alcohol as a tocolytic is now obsolete. (See all compounds classified as Tocolytic Agents.)|Drugs used to cause dilation of the blood vessels. (See all compounds classified as Vasodilator Agents.)|Drugs that selectively bind to and activate beta-adrenergic receptors. (See all compounds classified as Adrenergic beta-Agonists.)|Drugs that mimic the effects of stimulating postganglionic adrenergic sympathetic nerves. Included here are drugs that directly stimulate adrenergic receptors and drugs that act indirectly by provoking the release of adrenergic transmitters. (See all compounds classified as Sympathomimetics.)

Readily absorbed from the gastrointestinal tract.|Duration of action: 2 hours.|Time to peak effect: 30 minutes.|Onset of action: 10 minutes.

Duration of action is 10h.

This drug is classified as a beta receptor agonist.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. 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. 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. **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). **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.|The interaction of isoxuprine and nylidrin with alpha 1- and beta 2-adrenoreceptors in rat vas deferens was examined using radioligand binding assays and physiological studies in vitro. Isoxuprine and nylidrin have a greater affinity for binding to alpha 1 (isoxuprine KD = 59 + or - 15 nM; nylidrin KD = 41 + or - 3 nM) than beta 2-(isoxuprine KD = 3,900 + or - 500 nM; nylidrin KD = 900 + or - 50 nM) adrenoreceptors in rat vas deferens. Vas deferens from rats pretreated for 16-24 hr with reserpine (3 mg/kg i.p.) were exposed to 10 uM phenoxybenzamine for 15 min to inactivate alpha-adrenoreceptors. Under these conditions high concentrations of both isoxuprine and nylidrin relaxed vas deferens contracted with 55 mM K+, however the relaxation was not blocked by the beta-adrenoreceptor antagonist propranolol (10 uM). Both isoxuprine and nylidrin were potent competitive antagonists of alpha 1-adrenoreceptor mediated contraction of vas deferens. pA2 values for isoxuprine (6.9 + or - 0.05) and nylidrin (7.1 +or - 0.08) agreed well with KD values for binding to alpha 1-adrenoreceptors in vas deferens. The greater potency of isoxuprine and nylidrin in inhibiting alpha 1-adrenoreceptors than binding to beta 2-adrenoreceptors or causing nonspecific relaxation suggest that alpha-adrenoreceptor antagonist actions of these drugs may be important in their ability to inhibit smooth muscle tone.

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/OTHER TOXICITY INFORMATION/ Vasodilation of skeletal arteries and arterioles via beta-adrenergic receptor stimulation and possibly also a direct effect.|/OTHER TOXICITY INFORMATION/ Systolic pressure usually rises slightly and diastolic pressure falls; mean arterial pressure changes little. Cerebral blood flow may incr slightly.|/OTHER TOXICITY INFORMATION/ Actions ... follow pattern of beta-receptor stimulation but vasodilatation is resistant to doses of propranolol that block vasodilatation due to isoproterenol. Blood flow in muscle incr and peripheral resistance falls. Heart rate and cardiac output incr.

Arlidin

SKF-1700-A, Arlidin, Bufedon, Buphedrin, Dilatal, Dilatol, Dilatropon, Dilydrin, Opino, Perdilatal, Rudilin, and Rydrin. /Hydrochloride/|DILATYL, & VERINA; & BUPHENINE, NYLIDRIN & SUPRIFEN PSB AS THE HYDROCHLORIDE. /HYDROCHLORIDE/

Analyte: chloroquine; matrix: pharmaceutical preparation (solution); procedure: reversed-phase high-performance liquid chromatography with ultraviolet detection at 210 nm

METHOD FOR DETECTION OF NG QUANTITIES OF NYLIDRIN INVOLVES BETA-GLUCURONIDASE HYDROLYSIS, EXTRACTION WITH CHLOROFORM, DERIVATIZATION BY SILYLATION, & GAS-LIQ CHROMATOGRAPHY DETECTION.|Analyte: nylidrin; matrix: blood (plasma); procedure: high-performance liquid chromatography with electrochemical detection; limit of detection: 1 ng/mL

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