Nialamide

298.34

298.34

200-079-3

T2Q0RYM725

759298|124514

DTXSID1023362

White crystalline powder

N - Nervous system

2933399090

83.1

0.87

1.203g/cm3

151.6 °C

538.1ºC at 760mmHg

279.2ºC

1.589

ethanol: clear to hazy

−20°C

8.75X10-12 mm Hg at 25 deg C (est)

Oral-rat LD50: 1700 mg/kg; Oral-Mouse LD50; 590 mg/kg

Flammable; burning produces toxic nitrogen oxide fumes

Slightly bitter

Henry's Law constant =1.5X10-18 atm cu-m/mole at 25 °C (est)

pKa = 4.2 (puridine) (est)

174.3 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Hydroxyl radical reaction rate constant = 1.2X10-10 cu cm/molecule-sec at 25 °C (est)

III

6.1(b)

3249

3

20/21/22-36/37/38-40

22-26-36

NS1225000

Xn

Ventilated, low temperature and dry

P261-P280-P305 + P351 + P338

H302 + H312 + H332-H315-H319-H335-H351

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.

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P261, P264, P270, P271, P280, P281, P301+P312, P302+P352, P304+P312, P304+P340, P305+P351+P338, P308+P313, P312, P321, P322, P330, P332+P313, P337+P313, P362, P363, P403+P233, P405, and P501|Aggregated GHS information provided by 38 companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

moderately toxic

When administered orally to mice 1 hr before nialamide 100 mg/kg SC two non-selective and nine selective 5-HT uptake inhibitors enhanced the hypermotility produced by nialamide, whereas two inhibitors of NA uptake showed no influence on the nialamide response. Paroxetine was the most potent nialamide potentiator; 100% increase in motility response was obtained at 0.012 mg/kg. Pretreatment with the 5-HT2 antagonist ritanserin 1 and 10 mg/kg SC reduced the hypermotility produced by nialamide 200 mg/kg SC, but the 5-HT1 antagonist L-propranolol 10 mg/kg administered similarly was found inactive. Nialamide 100 mg/kg was given SC to groups of mice being treated for 4 weeks with paroxetine and lithium given through the diet. At daily intakes of paroxetine and lithium resulting in therapeutic plasma or serum levels a distinctive nialamide potentiation was found.

LD50 Mouse oral 590 mg/kg /from table/|LD50 Mouse iv 120 mg/kg /from table/|LD50 Mouse ip 200 mg/kg /from table/|LD50 Rabbit ip >150 mg/kg /from table/|For more Non-Human Toxicity Values (Complete) data for NIALAMIDE (6 total), please visit the HSDB record page.

Through a controlled double-blind study in 30 hospitalized patients affected with endogenous depression, the antidepressant action of the combination of nialamide + L-5-Hydroxytryptophan has been evaluated and compared with a control group which only received nialamide (+ placebo). The patients treated with nialamide + L-5-Hydroxytryptophan achieved a fuller recovery than those who were treated with nialamide alone. The treatment with nialamide + L-5-Hydroxytryptophan proved to have a shorter delay of onset. Side effects showed no marked differences except for the orthostatic hypotension which was less apparent in those patients treated with nialamide + L-5-Hydroxytryptophan. /Former use/

Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems. (See all compounds classified as Antidepressive Agents.)|A chemically heterogeneous group of drugs that have in common the ability to block oxidative deamination of naturally occurring monoamines. (From Gilman, et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p414) (See all compounds classified as Monoamine Oxidase Inhibitors.)

/OTHER TOXICITY INFORMATION/ Nialamide, an MAO inhibitor, was given per os (PO) to a normal man who volunteered in two separate trials (total intake 300 mg and 1000 mg, respectively), and his bufotenin excretion was followed by consecutive urine samples. In both experiments the excretion rose well above the values measured from the same test subject when not taking nialamide (median 0.089 nmol/mmol creatinine, range 0.002-1.78). At its highest, the excretion was 16.5 nmol/mmol creatinine, and the maximum urinary output was 495 nmoles (56 micrograms) in 24 hr. The levels of bufotenin in plasma required for the excretion of the latter amounts are not far from those that produce psychic symptoms in man.

Nialamide was one of the first MAOI (monoamine oxidase inhibitor) antidepressants. It is chemically related to iproniazide, another MAOI derived from isonicotinic acid. //|Time- and dose-response analyses were undertaken to investigate the effects of the substituted hydrazine monoamine oxidase (MAO) inhibitors iproniazid and nialamide on the following: MAO-A and -B activity; levels of gamma-aminobutyric acid (GABA), alanine (ALA), and the neurotransmitter amines dopamine, noradrenaline, and 5-hydroxytryptamine (serotonin) and their acid metabolites; and the activity of GABA-transaminase and ALA-transaminase. The results showed that these drugs are relatively potent MAO inhibitors but, unlike the unsubstituted hydrazine MAO inhibitor phenelzine, they do not produce increased GABA and ALA levels in brain. These experiments suggest that a free hydrazine group is necessary for MAO inhibitors to also have marked effects on GABA and ALA.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/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/

Nialamide

Trade Names: Niamid, Nuredal, and Surgex.

Withdrawn from the Canadian, US, and UK markets in 1963 due to interactions with food products containing tyrosine.

Analyte: nialamide; matrix: blood (plasma, whole); procedure: high-performance liquid chromatography with diode array detection and ultraviolet detection at 264 nm; limit of detection: <120 ng/mL

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