Nonivamid

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals

Fragrance Ingredient (Nonanoyl 4-hydroxy-3-methoxybenzylamide) -> IFRA transparency List

Fragrance

Soluble in water (slightly)

slightly

Slightly soluble in water

Soluble (in ethanol)

This chemical does not meet GHS hazard criteria for 0.3% (5 of 1513) of reports.

Danger

H301 (85.7%): Toxic if swallowed [Danger Acute toxicity, oral]

P233, P260, P261, P264, P264+P265, P270, P271, P272, P280, P284, P301+P316, P302+P352, P304+P340, P305+P351+P338, P305+P354+P338, P317, P319, P321, P330, P332+P317, P333+P317, P337+P317, P342+P316, P362+P364, P403, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 1513 reports by companies from 17 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Chemical: Nonanamide, N-[(4-hydroxy-3-methoxyphenyl)methyl]-

Commission Regulation (EC) No 1565/2000 (Repealed by Com. Implementing Reg. (EU) No 872/2012)

Nonivamide: Does not have an individual approval but may be used under an appropriate group standard

Effects sensory neurons; [ChemIDplus] Causes lung inflammation in acute inhalation studies of mice; [RTECS] Safe when used as a flavoring agent in food; [JECFA] A skin and strong eye irritant; May cause skin sensitization; [Sigma-Aldrich MSDS] Search for (2444-46-4[EC/RN Number]) AND (sensitizer OR sensitization OR dermatitis OR allergic): no results; [PubMed]

Nonivamide is a naturally occurring analog of [DB06774], isolated from peppers, described to produce effects similar to [DB06774]. It is an agonist of the VR1 (vanilloid/TRPV1 receptor). It serves as a transient agonist of these receptors, which are potentiated by pro-inflammatory drugs, a phenomenon that leads to thermal hyperalgesia, or increased heat sensation. Nonivamide has been shown to stimulate afferent neurons with about half the potency of [DB06774]. Agonism of the VR1 (TRPV1) (vanilloid) receptor by Nonivamide was demonstrated to induce the release of Ca2+ from the endoplasmic reticulum (ER) of human lung cells, producing ER stress and cell death [MSDS]. Nonivamide, like other capsaicinoids, acts on the vanilloid receptors located in the peripheral afferent nerve fibers, providing short-acting irritant and algesic properties. Applied dermally, these substances act by stimulating sensitive chemoreceptors of the skin and by reflex, hyperemia and a local elevation in temperature. After repetitive administration, capsaicinoids have been reported to lead to desensitization to nociceptive stimuli possibly by long-acting depletion of peptide neurotransmitters (substance P) from peripheral sensory neurons. Capsaicinoids can modulate muscle tone (in bladder, bronchus etc.). Intravenous injection of nonivamide to rats (10 μg/kg) has been found to lead to bradycardia. The cardiovascular effects are partly explained by substance P release. Nonivamide given to rats subcutaneously (1 mg/kg) was found to cause body temperature decrease, vasodilatation, and increased salivation. Capsaicinoids have shown to illicit bronchospastic effects in guinea pigs. Capsaicin and its analogs were reported to increase barbiturate sleeping time in rats by interacting with hepatic metabolizing enzymes.

Limited information is available on pharmacokinetics and metabolism of nonivamide. For the closely related [DB06774] and other capsaicinoids, gastrointestinal absorption is rapid and almost entirely complete in studies of rats (oral dose of about 10 to 15 mg/kg of combined capsaicin and dihydrocapsaicin) with about 85% of the dose being absorbed within 3 hours. Both substances undergo first-pass metabolism in the liver and partly metabolized at the site of absorption.