| Identification | Back Directory | [Name]
Biguanide | [CAS]
56-03-1 | [Synonyms]
diguanide
Biguanide
guanylguanidine
amidinoguanidine
2-Amidinoguanidine
2-carbamimidoylguanidine
IMidodicarboniMidicdiaMide
1-(Diaminomethylene)guanidine
2,4-Diimino-1,3,5-triazapentane
1-(Diaminomethylidene)guanidine | [EINECS(EC#)]
200-251-8 | [Molecular Formula]
C2H7N5 | [MDL Number]
MFCD00045592 | [MOL File]
56-03-1.mol | [Molecular Weight]
101.11 |
| Hazard Information | Back Directory | [Chemical Properties]
solid | [Description]
French physician Jean Sterne published the first clinical trial in
1957 suggesting metformin as a treatment for diabetes. The
United Kingdom introduced this drug in 1958 followed by
Canada in 1972, and the United States in 1995. As of 2010,
metformin was one of only two oral antidiabetics in the World
Health Organization model list of essential medicines, the
other being glibenclamide. Metformin is believed to enjoy the
popularity of being the most widely prescribed antidiabetic
drug in the world. It has been estimated that the United States
alone has filled nearly a million prescriptions in 2010 for its
generic formulations. Biguanides are not hypoglycemic
agents; rather they promote euglycemia (antihyperglycemic).
Biguanides are used both as monotherapy and in combination
with other oral hypoglycemic agents to control hyperglycemia.
Although very safe in most instances, the major toxicity from
acute or chronic use of biguanides has been reported to be
lactic acidosis. In fact, the high rate of severe lactic acidosis was
the only major cause of withdrawal of phenformin from the US
market in 1976. | [Uses]
Biguanides are used as an oral drug for the management of
mild to moderately severe noninsulin-dependent diabetes
mellitus, or NIDDM, (Type II) in obese or overweight patients
who are usually above 40 years of age. It is important that for
the administration of this drug the disease should have adult
onset. Polymeric biguanides were originally developed as
a presurgery antimicrobial scrub and in 1977, it was introduced
in the market for treating pools and spas as a disinfectant under
the trade name Baquacil. The US Environmental Protection
Agency approved this agent as the only nonhalogen sanitizer of
pools and spas. Biguanide itself is combined with algaecides
and hydrogen peroxide for periodic oxidation of pools and
spas. Biguanides are incompatible with chlorine, ozone,
detergents, and ionizers, but are compatible with water ion
balancing chemicals. Biguanide in the form of polyaminopropyl
biguanide serves as a disinfectant, and preservative
for skin disinfection, contact lens cleaning solutions, and
deodorant body sprays. Biguanides reduce the surface tension
of water, which gives it a smoother feeling. They are stable in
sunlight and temperature. At recommended concentrations
when used in pools and spas, biguanides do not irritate the skin
or eyes and do not corrode the pool equipment. | [Definition]
ChEBI: Biguanide is a member of guanidines. | [Environmental Fate]
Globally, hundreds of millions of patients are prescribed this
drug annually. Metformin was discovered before the era of
target-based drug discovery, and its molecular mechanism of
action remains an important focus of diabetes research.
Advances in our understanding of metformin’s molecular
targets are likely to enable target-based identification of secondgeneration
drugs with similar properties, a development that
has been a difficult task until now. Besides its potent antidiabetic
properties, Metformin’s potential as a targeted anticancer
agent is being explored in a number of laboratories throughout
the world. | [Purification Methods]
Crystallise biguanide from EtOH. It gives a red Cu derivative, and it forms salts with many metals. The monohydrochloride has m 235o [38664-03-8] and the dihydrochloride forms plates with m 248o (213-214o, also reported) [25836-74-2]. [Beilstein 3 H 93, 3 I 44, 3 II 76, 3 III 171, 3 IV 162.] | [Toxicity evaluation]
Biguanides, salts of biguanide, or biguanide-like compounds
such as Metformin hydrochloride production and use as an
antidiabetic medication may result in its release to the
environment through various waste streams. Metformin
hydrochloride is expected to exist in the dissociated form as
metformin in the environment. If released to air, an estimated
vapor pressure of 0.0034 mm Hg at 25 °C indicates
metformin will exist solely in the vapor phase in the
ambient atmosphere. Metformin, when in vapor phase, is
expected to be degraded in the atmosphere by reaction with
photochemically-produced hydroxyl radicals; the half-life for
this reaction in air is estimated to be 15 min. If released to
soil, metformin is expected to have high mobility based on
an estimated Koc of 110. Volatilization from moist soil
surfaces is not expected to be an important fate process
based on an estimated Henry’s law constant of
7.6×10-16 atm-cu m mol-1. The pKa of metformin is 12.4,
indicating that this compound will primarily exist in cation
form in the environment, and cations generally adsorb to
organic carbon and clay more strongly than their neutral
counterparts. Based on metformin’s vapor pressure, it is not
expected to volatilize from dry soil surfaces. Based on the
estimated Koc of metformin, it is not expected to adsorb to
suspended solids and sediment if released into water. Volatilization
from water surfaces is not expected to be an
important fate process based on this compound’s estimated
Henry’s law constant. Furthermore, a pKa of 12.4 indicates
metformin will exist almost entirely in the ionized form at
pH values of 5–9. An estimated bioconcentration factor of
3.2 suggests the potential for bioconcentration in aquatic
organisms is low. Hydrolysis is not expected to be an
important environmental fate process since this compound
lacks functional groups that hydrolyze under environmental
conditions. Occupational exposure to metformin hydrochloride
may occur through inhalation and dermal contact
with this compound at workplaces where metformin
hydrochloride is produced or used. |
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