Pilocarpine nitrate

[Description]:

Pilocarpine nitrate is a selective M3-type muscarinic acetylcholine receptor (M3 muscarinic receptor) agonist.

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> mAChR

Signaling Pathways >> Neuronal Signaling >> mAChR

Research Areas >> Neurological Disease

[Target]

M3 muscarinic receptor[1]

[In Vitro]

To evaluate the cytotoxicity of Pilocarpine, the morphology and viability of human corneal stromal (HCS) cells are examined by light microscopy and MTT assay, respectively. Morphological observations show that HCS cells exposed to Pilocarpine at a concentration from 0.625 to 20 g/L exhibit dose- and time-dependent proliferation retardation and morphological abnormality such as cellular shrinkage, cytoplasmic vacuolation, detachment from culture matrix, and eventually death, while no obvious difference is observed between those exposed to Pilocarpine below the concentration of 0.625 g/L and controls. Results of MTT assay reveal that the cell viability of HCS cells decrease with time and concentration after exposing to Pilocarpine above the concentration of 0.625 g/L (P<0.01 or 0.05), while that of HCS cells treated with Pilocarpine below the concentration of 0.625 g/L show no significant difference to controls[2]. The partial muscarinic agonist, Pilocarpine, evokes concentration-dependent relaxation with an EC50 of 2.4 mM in isolated segments of rat tail artery that were constricted with Penylephrine (10 to 200 nM)[3].

[In Vivo]

The Pilocarpine-induced saliva secretion of the control rats (CN) and exercised (EX) rats is examined. A significantly greater amount of saliva is induced by Pilocarpine in the EX rats than in the CN rats (P<0.01). Conversely, the Na+ concentration in the saliva of the EX rats is significantly lower than that of the CN rats (P<0.05)[1].

[Cell Assay]

Cell viability is determined by MTT assay. Briefly, HCS cells are inoculated into a 96-well culture plate (Nunc) at a density of 1×104 cells/100 µL/well, and are cultured and treated. At a 4h interval, the Pilocarpine (0.625 to 20 g/L)-containing medium is replaced entirely with 100 µL serum-free DMEM/F12 medium containing 1.0 g/L MTT, and the cells are incubated at 37°C in the dark for 4h. After the MTT-containing medium is discarded with caution, 150 µL DMSO is added to dissolve the produced formazan crystals at 37°C in the dark for 15 min, and the absorbance at 490 nm is measured with a Multiskan GO microplate reader[2].

[Animal admin]

Rats[1] Male, 10-week-old Wistar rats are assigned to one of two groups, exercise (EX, n=6) and control (CN, n=6). The EX rats are kept for 40 days in cages with a running wheel (SN-451), allowing them to undertake voluntary exercise, while the CN rats are kept in cages with the running wheel locked. On the 40th day, Pilocarpine-induced saliva is measured as follows. Briefly, the rats are anesthetized, preweighed cotton was placed in their mouths sublingually, and Pilocarpine (0.5 mg/kg) is intraperitoneally injected to induce saliva secretion. Each cotton ball is then changed every 10 min for 1 h. The collected cotton balls are weighed again, and the mass of saliva secreted is calculated by subtracting the initial from the final weight.

[References]

[1]. Matsuzaki K, et al. Daily voluntary exercise enhances pilocarpine-induced saliva secretion and aquaporin 1 expression in rat submandibular glands. FEBS Open Bio. 2017 Dec 7;8(1):85-93.

[2]. Yuan XL, et al. Cytotoxicity of pilocarpine to human corneal stromal cells and its underlying cytotoxic mechanisms. Int J Ophthalmol. 2016 Apr 18;9(4):505-11.

[3]. Tonta MA, et al. Pilocarpine-induced relaxation of rat tail artery by a non-cholinergic mechanism and in the absence of an intact endothelium. Br J Pharmacol. 1994 Jun;112(2):525-32.

[Related Small Molecules]

[ Boiling Point ]:
520.5ºC at 760 mmHg

[ Melting Point ]:
173,5-174°C

[ Molecular Formula ]:
C₁₁H₁₇N₃O₅

[ Molecular Weight ]:
271.27000

[ Flash Point ]:
268.6ºC

[ Exact Mass ]:
271.11700

[ PSA ]:
110.17000

[ LogP ]:
1.33730

[ Vapour Pressure ]:
1.16E-11mmHg at 25°C

[ Index of Refraction ]:
81 ° (C=2, H2O)

[ Storage condition ]:
2-8°C

[ Water Solubility ]:
H2O: 0.1 g/mL, clear, very faintly yellow

CHEMICAL IDENTIFICATION

RTECS NUMBER :: TK1455000

CHEMICAL NAME :: Pilocarpine, mononitrate

CAS REGISTRY NUMBER :: 148-72-1

LAST UPDATED :: 199701

DATA ITEMS CITED :: 10

MOLECULAR FORMULA :: C11-H16-N2-O2.H-N-O3

MOLECULAR WEIGHT :: 271.31

WISWESSER LINE NOTATION :: T5OVTJ C2 D1- ET5N CNJ A1 &WNO

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 911 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - fluid intake Kidney, Ureter, Bladder - urine volume decreased

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 345 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 15600 mg/kg/15W-I

TOXIC EFFECTS :: Gastrointestinal - hypermotility, diarrhea Kidney, Ureter, Bladder - urine volume increased Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 2200 mg/kg

SEX/DURATION :: female 1-22 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - skin and skin appendages

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: Mutation test systems - not otherwise specified

MUTATION DATA

TEST SYSTEM :: Rodent - mouse

DOSE/DURATION :: 8 mg/kg

REFERENCE :: MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 344,103,1995 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 81934 No. of Facilities: 42 (estimated) No. of Industries: 2 No. of Occupations: 4 No. of Employees: 980 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - 81934 No. of Facilities: 22 (estimated) No. of Industries: 1 No. of Occupations: 2 No. of Employees: 1525 (estimated) No. of Female Employees: 1273 (estimated)

[ Symbol ]:

GHS06

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H300 + H330

[ Precautionary Statements ]:
Missing Phrase - N15.00950417-P260-P304 + P340 + P310-P403 + P233

[ Personal Protective Equipment ]:
Eyeshields;Faceshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges

[ Hazard Codes ]:
Xn: Harmful;

[ Risk Phrases ]:
R22

[ Safety Phrases ]:
S1-S25-S45

[ RIDADR ]:
3087

[ WGK Germany ]:
3

[ RTECS ]:
TK1455000

[ Packaging Group ]:
III

[ Hazard Class ]:
6.1(b)

[ HS Code ]:
2934999090

Click to get detail synthetic route

[ HS Code ]: 2934999090

[ Summary ]:
2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Chemical genetics reveals a complex functional ground state of neural stem cells.

Nat. Chem. Biol. 3(5) , 268-273, (2007)

The identification of self-renewing and multipotent neural stem cells (NSCs) in the mammalian brain holds promise for the treatment of neurological diseases and has yielded new insight into brain canc...

Function of inhibitory micronetworks is spared by Na+ channel-acting anticonvulsant drugs.

J. Neurosci. 34(29) , 9720-35, (2014)

The mechanisms of action of many CNS drugs have been studied extensively on the level of their target proteins, but the effects of these compounds on the level of complex CNS networks that are compose...

Development and characterization of pilocarpine loaded Eudragit nanosuspensions for ocular drug delivery.

J. Biomed. Nanotechnol. 9(1) , 124-31, (2013)

With aim of improving the availability of drug at intraocular level and to reduce the frequency of drug administration, pilocarpine nitrate nanosuspensions were made from inert polymer resin (Eudragit...

Names

Biological Activity

Chemical & Physical Properties

Toxicological Information

CHEMICAL IDENTIFICATION

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

MUTATION DATA

Safety Information

Synthetic Route

Click to get detail synthetic route

Customs

Articles

Related Compounds