Guanidine

In water, 1,840 mg/L at 25 °C

829 mg/mL

50 °C

182.3 °C

Deliquescent solid; Absorbs carbon dioxide from the air; [Merck Index]

Solid

Positive

1.95

2.7

Agilent XCT

Electrospray ionization

formic acid (5.3nM)

12.5

pKa = 12.5

This chemical does not meet GHS hazard criteria for 40% (2 of 5) of reports.

Danger

H225 (40%): Highly Flammable liquid and vapor [Danger Flammable liquids]

P210, P233, P240, P241, P242, P243, P260, P261, P262, P264, P264+P265, P270, P271, P280, P301+P316, P301+P317, P301+P330+P331, P302+P352, P302+P361+P354, P303+P361+P353, P304+P340, P305+P351+P338, P305+P354+P338, P308+P316, P316, P317, P321, P330, P332+P317, P337+P317, P361+P364, P362+P364, P363, P370+P378, P403+P233, P403+P235, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 5 reports by companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

The chloride salt is highly irritating to the skin and eyes of rabbits and is not a skin sensitizer in guinea pigs; Symptoms of severe oral intoxication include muscle tremors and convulsive contractions, salivation, vomiting, hypoglycemia, and circulatory disturbances; [HSDB]

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl guanidine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Guanidine Hydrochloride/

Flam. Liq. 2 (40%)

Acute toxicity (Oral) - Category 4

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.

The characteristics of guanidine uptake in brush-border membrane vesicles isolated from rabbit renal cortex were investigated ... Guanidine uptake was only minimally inhibited by organic cations such as tetraethylammonium, N1-methylnicotinamide, and choline, but many other organic cations such as amiloride, clonidine, imipramine, and harmaline caused considerable inhibition. Uptake of radiolabeled guanidine was inhibited more effectively by guanidine than by tetraethylammonium, whereas uptake of radiolabeled tetraethylammonium was inhibited more effectively by tetraethylammonium than by guanidine. beta-Lactam antibiotics did not inhibit guanidine uptake but did inhibit tetraethylammonium uptake. Kinetic analysis showed that there were at least two kinetically distinct carrier systems for guanidine uptake, whereas tetraethylammonium uptake occurred via a single carrier system ...

Concurrent therapy with other drugs that may cause bone-marrow suppression should be avoided. /Guanidine hydrochloride/

LC50; Species: Cloeon dipterum (Mayfly, nymphs, length 9.3 mm, weight 5.6 mg); Conditions: freshwater, 25 °C; Concentration: 22000 ug/L for 3 hr /Conditions of bioassay not specified in source examined/

LC50; Species: Cloeon dipterum (Mayfly, nymphs, length 9.3 mm, weight 5.6 mg); Conditions: freshwater, 25 °C; Concentration: 15000 ug/L for 6 hr /Conditions of bioassay not specified in source examined/

LC50; Species: Cloeon dipterum (Mayfly, nymphs, length 9.3 mm, weight 5.6 mg); Conditions: freshwater, 25 °C; Concentration: 7200 ug/L for 24 hr /Conditions of bioassay not specified in source examined/

LC50; Species: Cloeon dipterum (Mayfly, nymphs, length 9.3 mm, weight 5.6 mg); Conditions: freshwater, 25 °C; Concentration: 2000 ug/L for 48 hr /Conditions of bioassay not specified in source examined/

LC50 Leuciscus idus (ide) 1758 mg/L/48 hr /Conditions of bioassay not specified in source examined/ /Guanidine chloride/

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 20(SRC), determined from a structure estimation method(2), indicates that guanidine is expected to have very high mobility in soil(SRC). However, guanidine has a pKa of 12.5(3) and should exist almost entirely as a cation under environmental conditions (pH 5-9)(SRC). As a result, guanidine may have greater adsorption and less mobility than its estimated Koc value indicates since cations generally adsorb more strongly to soils containing organic carbon and clay than neutral species(4). Volatilization from moist soil surfaces is not an important environmental fate process since cations do not volatilize(SRC). The potential to volatilize from dry soil surfaces exists based upon an estimated vapor pressure of 2.2 mm Hg(SRC), determined from a fragment constant method(5). Guanidine was degraded in soil samples incubated under aerobic conditions at varying rates as a function of the initial starting concentration(6). At an initial concentration of 10 mg/kg, guanidine was 78% biodegraded after 10 days; however, at an initial concentration of 400 mg/kg, guanidine was 62% biodegraded after 25 days(6).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 20(SRC), determined from a structure estimation method(2), indicates that guanidine is not expected to adsorb to suspended solids and sediment(SRC). However, guanidine has a pKa of 12.5(3) and should exist almost entirely as a cation under environmental conditions (pH 5-9)(SRC). As a result, guanidine may have greater adsorption to suspended solids and sediment than its estimated Koc value indicates(SRC). Volatilization of guanidine from water surfaces will not be an important fate process, since cations do not volatilize(SRC). According to a classification scheme(4), BCF values in the range of <0.1 to 0.1 measured in fish(5), suggest bioconcentration in aquatic organisms is low(SRC). Complete guanidine degradation in stream water samples obtained near a nitroguanidine production facility was observed in 20 days after an initial lag period 11 days and 68 days following a lag period 52 days(5).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), guanidine, which has an estimated vapor pressure of 2.2 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase guanidine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 9 hours(SRC), calculated from its rate constant of 4.2X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Guanidine does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(4).

Uremic toxins such as guaniidine are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (A7868). Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species (A7869).

As a uremic toxin, this compound can cause uremic syndrome. Uremic syndrome may affect any part of the body and can cause nausea, vomiting, loss of appetite, and weight loss. It can also cause changes in mental status, such as confusion, reduced awareness, agitation, psychosis, seizures, and coma. Abnormal bleeding, such as bleeding spontaneously or profusely from a very minor injury can also occur. Heart problems, such as an irregular heartbeat, inflammation in the sac that surrounds the heart (pericarditis), and increased pressure on the heart can be seen in patients with uremic syndrome. Shortness of breath from fluid buildup in the space between the lungs and the chest wall (pleural effusion) can also be present.

Using a structure estimation method based on molecular connectivity indices(1), the Koc of guanidine can be estimated to be 20(SRC). According to a classification scheme(2), this estimated Koc value suggests that guanidine is expected to have very high mobility in soil(SRC). The pKa of guanidine is 12.5(3), indicating that this compound will exist almost entirely as a cation in the environment(SRC). As a result, guanidine may have greater adsorption and less mobility than its estimated Koc value indicates since cations generally adsorb more strongly to soils containing organic carbon and clay than neutral species(4).

/SIGNS AND SYMPTOMS/ Severe guanidine intoxication is characterized by nervous hyperirritability, fibrillary tremors and convulsive contractions of muscle, salivation, vomiting, diarrhea, hypoglycemia, and circulatory disturbances. Administration of intravenous calcium gluconate may control the neuromuscular and convulsive symptoms and provide some relief of other toxic manifestations. /Guanidine hydrochloride/

/CASE REPORTS/ A 43-year-old man with Eaton-Lambert syndrome developed chronic interstitial nephritis after 4 years of guanidine hydrochloride therapy. The diagnosis of Eaton-Lambert syndrome was confirmed by clinical neurophysiologic studies and by intracellular electrode studies of end-plate potentials from an intercostal muscle biopsy. Because guanidine had toxic effects in this patient, an alternative form of therapy was tried. /Guanidine hydrochloride/

/ALTERNATIVE and IN VITRO TESTS/ Plasma proteins in hemodialysis patients display a significant increase in deamidated/isomerized Asx (asparagine and aspartic acid) content, a marker of protein fatigue damage ... The deamidated/isomerized Asx content of normal plasma incubated with several uremic toxins for 24 hr, 72 hr, and 7 days was measured, identifying a group of toxins that were able to elicit this kind of damage. Uremic toxins were also incubated with purified human albumin, and dose-response experiments with the two most toxic agents in terms of protein damage (guanidine and guanidinopropionic acid) were carried out ... Among the uremic toxins that are able to elicit protein damage, guanidine produced a dose-dependent increase in protein damage. No difference was found after a hemodialysis session.

/ALTERNATIVE and IN VITRO TESTS/ Plasma levels of endogenous guanidine compounds are increased in various pathologic conditions, including chronic renal failure. In the present study ... the effects of some of these compounds on basal and stimulated nitric oxide activity in human renal arteries /were tested/ ... Rings from human renal arteries were obtained from 22 patients undergoing nephrectomy ... The effects of N(G)-monomethyl-L-arginine (L-NMMA), N(G),N(G)-dimethyl-L-arginine (asymmetrical dimethylarginine (ADMA)), aminoguanidine (AG), and methylguanidine (MG) on artery rings under basal and stimulated conditions /were studied/ ... In precontracted arteries, L-NMMA (1 umol/L to 1 mmol/L) and ADMA (1 umol/L to 3 mmol/L) caused concentration- and endothelium-dependent contractions (median effective concentrations (EC50) = 13.3 umol/L and 17.5 umol/L, respectively; Emax = 15 + or - 4% and 17 + or - 4% of the response to 100 mmol/L KCl, respectively). Aminoguanidine (0.01 to 3 mmol/L) and MG (0.01 to 3 mmol/L) produced endothelium-independent contractions (Emax = 9 + or -3% and 16 + or - 2% of the response to 100 mmol/L KCl, respectively). L-arginine (1 mmol/L) but not D-arginine (1 mmol/L) prevented the contractions by L-NMMA and ADMA, but did not change contractions induced by AG and MG. In precontracted arteries, the relaxation to acetylcholine was decreased but not abolished by L-NMMA and ADMA. The remaining relaxation was reduced by charybdotoxin (0.1 mol/L) and tetraethylammonium (1 mmol/L) ... The results demonstrate that L-NMMA and ADMA reduce basal and stimulated nitric oxide activity in human renal arteries. An increase in the plasma concentrations of methylarginines associated with renal disease should be considered as a risk factor for endothelial dysfunction and abnormal vasomotor tone in human renal arteries. /Endogenous guanidine compounds/

/OTHER TOXICITY INFORMATION/ Guanidino compounds are known as uremic toxins which increase in the blood of patients with renal failure. Guanidino succinic acid (GSA) and methyl guanidine (MG) ... reflect the pathological stage of nephritis. GSA correlates well with blood urea nitrogen and therefore indicates the reduction of renal function. MG does not appear in the early stage of renal failure and abruptly increases at the stage of serious uremia. /Guanidino compounds/

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl guanidine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Guanidine Hydrochloride/

Guanidine apparently acts by enhancing the release of acetylcholine following a nerve impulse. It also appears to slow the rates of depolarization and repolarization of muscle cell membranes. /Guanidine hydrochloride/

Guanidine-induced alterations in substrate dependent kinetics of hepatic and renal succinate dehydrogenase (SDH) have been investigated under in vitro conditions. Guanidine hydrochloride (GuHCl) induced a mixed type of inhibition by decreasing the maximal velocity (Vmax) and increasing the Michaelis-Menten constant (Km). The competitive (Ki) and non-competitive (Ki) inhibitory constants ... showed that the inhibitory influence of GuHCl is more due to decreased enzyme substrate affinity rather than reduction in the active site density of the enzyme as revealed by low Ki values. /Guanidine hydrochloride/

Not metabolized.

Not metabolized. Half Life: 7-8 hours

JU58VJ6Y3B

GUANIDINE

Established Pharmacologic Class [EPC] - Acetylcholine Releasing Agent

Physiologic Effects [PE] - Increased Acetylcholine Activity

Guanidine is an Acetylcholine Releasing Agent. The physiologic effect of guanidine is by means of Increased Acetylcholine Activity.

Rapidly absorbed and distributed

Accumulation of specific guanidine compounds (GCs) has been related to neurological, cardiovascular, hematological, and immunological complications of renal failure ... The obvious increases of urea, guanidinosuccinic acid, creatinine, guanidine, methylguanidine, and N(G)N(G)-dimethylarginine (symmetrical dimethylarginine) seen in blood of oldest heterozygous and younger homozygous polycystic kidney disease (PKD) rats were largely within the same range as those found in the studied human PKD population, especially in patients with a glomerular filtration rate below 60 mL/min/1.73 sq m. The decreased levels of plasma guanidinoacetic acid seen at end-stage renal disease in homozygous and oldest heterozygous PKD/Mhm rats were also observed in serum of patients with a glomerular filtration rate below 20 mL/min/1.73 sq m ... /Guanidino compounds/

Brush-border membrane vesicles were prepared from donor human kidneys ... Uptake of (14)C-guanidine ... in the vesicles, as determined by rapid filtration, was significantly greater in the presence of an outwardly-directed proton gradient, at all early time points, than in the absence of the gradient ... Evidence was obtained suggesting that the transporter for guanidine is distinct from the previously described organic cation proton antiporter for TEA. /Tetraethylammonium/

The characteristics of guanidine uptake in brush-border membrane vesicles isolated from rabbit renal cortex were investigated. Guanidine uptake was markedly stimulated by an outwardly directed H+ gradient, resulting in a transient uphill transport. This stimulation was not due to an inside-negative, H+-diffusion potential because an ionophore-induced H+-diffusion potential and a K+-diffusion potential (both inside-negative) failed to enhance guanidine uptake. The H+ gradient itself appeared to be the driving force for the uptake ...

... The plasma, erythrocyte, and urinary concentration of guanidino compounds in 30 hemodialysis patients and 15 patients with chronic renal failure who had not undergone hemodialysis /were determined/ ... Plasma levels of taurocyamine, guanidinosuccinic acid, alpha-N-acetyl-L-arginine, creatine, guanidinobutyric acid, guanidine, and methylguanidine were significantly increased in patients with chronic renal failure with or without hemodialysis. In contrast, plasma guanidinoacetic acid concentrations were significantly decreased. Erythrocyte concentrations of creatinine, guanidinosuccinic acid, guanidine and methylguanidine were also markedly elevated. No correlation was observed between plasma creatinine concentration and erythrocyte concentration of guanidinosuccinic acid or methylguanidine. However, there was a significant correlation between plasma and erythrocyte methylguanidine, and between plasma and erythrocyte guanidinosuccinic acid. /Guanidino compounds/

For more Absorption, Distribution and Excretion (Complete) data for GUANIDINE (7 total), please visit the HSDB record page.

A strong organic base present in turnip juice, mushrooms, corn germ, rice hulls, mussels, and earthworms; Used as a therapeutic cholinergic; [Merck Index] Found in urine as a product of protein metabolism; Used in laboratory research, to treat myasthenia, and as a fluorescent probe in HPLC; [ChemIDplus] Used to make munitions, polymeric resins, flame retardants, and pharmaceuticals; [HSDB]

Organic synthesis

Starting material for munitions, polymeric resins, flame retardants, and pharmaceuticals.

For the reduction of the symptoms of muscle weakness and easy fatigability associated with the myasthenic syndrome of Eaton-Lambert. It is not indicated for treating myasthenia gravis.

From ammonium thiocyanate or thiourea + ammonia

(1) By heating calcium cyanamide with ammonium iodide. (2) By treating urea with ammonia under pressure.

Free guanidine can be isolated from guanidine salts by reaction with a strong base such as an alkali metal hydroxide or methoxide. After removal of the precipitated salt the free guanidine base is obtained as colorless, waxy, very hygroscopic crystals.