HuagongsheHuagongshe Chemie-Druckbericht · Nur für Forschungszwecke
Pilocarpin
actone · Pilocarpin · (3S,4R)-3-ethyl-4-((1-Methyl-1H-iMidazol-5-yl)Methyl)dihydrofuran-2(3H)-one · Ocusert · Syncarpine · pilokarpol · Pilokarpin · Pilocarpol
Identifikatoren & physikalische Daten
| CAS No. | 54-71-7 |
|---|---|
| Summenformel | C11H16N2O2 |
| Durchschnittliche Molmasse | 208,26 g/mol |
| Monoisotopische Masse | 208,12117776 g/mol |
| SMILES | CC[C@@H]1C(=O)OC[C@@H]1Cc1cncn1C |
| InChIKey | QCHFTSOMWOSFHM-WPRPVWTQSA-N |
| PubChem CID | 5910 |
| ChEMBL | CHEMBL550 |
| ChEBI | CHEBI:8207 |
| EC No. | 202-128-4 |
| DTXSID | DTXSID1021162 |
| Lokaler Name | Pilocarpin |
Chemische & physikalische Eigenschaften
| XLogP | 1,1 |
|---|---|
| Polarare Oberfläche (TPSA) | 44,1 |
| H-Brücken-Donoren | 0 |
| H-Brücken-Akzeptoren | 3 |
| Frei drehbare Bindungen | 3 |
| Schwere Atome | 15 |
| Formalladung | 0 |
| Komplexität | 245 |
| LogP (Verteilungskoeffizient) | -3.031.1 |
| Color/Form | OIL OR CRYSTALSNEEDLES |
| Löslichkeit | FREELY SOL IN ETHANOLINSOL IN DIETHYL ETHER /HCL/SOL IN WATER, ALC, CHLOROFORMSPARINGLY SOL IN ETHER, BENZENEALMOST INSOL IN PETROLEUM ETHERSOL IN ETHANOL, DIETHYL ETHER2.07e+00 g/LChloroform (Sparingly, Sonicated), Methanol (Slightly) |
| Siedepunkt | 260 °C @ 5 MM HG (PARTIAL CONVERSION TO ISOPILOCARPINE)bp5 260° (partial conversion to isopilocarpine) |
| Decomposition | ON HEATING TO DECOMP, EMITS TOXIC FUMES OF NO(X). |
| Schmelzpunkt | 195-20534 °C34° |
| Optical Rotation | SPECIFIC OPTICAL ROTATION: +106 DEG @ 18 °C/D (2%) |
| Physical Description | Solid |
| Stability/Shelf Life | HYGROSCOPIC. /HCL/SENSITIVE TO LIGHT.STABLE IN AIR BUT AFFECTED BY LIGHT. /NITRATE/ |
| Dissociation Constants | PK1= 7.15PK2= 12.57 @ 20 °C |
| Collision Cross Section | 151.18 Ų [M+K]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]139.67 Ų [M+H-H2O]+ [CCS Type: TW145.44 Ų [M+H]+ [CCS Type: TW148.74 Ų [M+Na]+ [CCS Type: TW |
| Other Experimental Properties | WHITE CRYSTALSSLIGHTLY BITTERMP: 195-198 °CALSO GIVEN AS 204-205 °C1 G DISSOLVES IN 0.3 ML WATER, 3 ML ALCOHOL, 366 ML CHLOROFORMINSOL IN ETHER/HCL/ODORLESS, FAINTLY BITTER CRYSTALSSOLN ACID TO LITMUSPKA1= 6.8, PKA2= 1.3 /HCL/MP: 173.5-174.0 °C DECOMPSPECIFIC OPTICAL ROTATION: +77 DEG TO +83 °FOR D (SODIUM) LINE (10%)1 G DISSOLVES IN 4 ML WATER, 75 ML ALCOHOLINSOL IN CHLOROFORM, ETHER /NITRATE/SOL ARE ACID TO LITMUS /NITRATE/WHITE POWDER OR CRYSTALS FROM ALC /NITRITE/ |
| Dichte | 1.1123 (rough estimate) |
| Brechungsindex | 1.5000 (estimate) |
| pKa (Säurekonstante) | 6.87(at 30℃) |
| Aggregatzustand | 34°C Liquid |
| Farbe | Colorless to light yellow |
| InChI | InChI=1S/C11H16N2O2/c1-3-10-8(6-15-11(10)14)4-9-5-12-7-13(9)2/h5,7-8,10H,3-4,6H2,1-2H3/t8-,10-/m0/s1 |
| InChIKey | QCHFTSOMWOSFHM-WPRPVWTQSA-N |
| SMILES | O1C[C@H](CC2N(C)C=NC=2)[C@H](CC)C1=O |
| LogP (Verteilungskoeffizient) | 0.120 |
| CAS Datenbank | 92-13-7(CAS DataBase Reference) |
| EPA chemische Informationen | 2(3H)-Furanone, 3-ethyldihydro-4-[(1-methyl-1H-imidazol-5-yl)methyl]-, (3S,4R)- (92-13-7) |
Sicherheit & Vorschriften
| GHS-Einstufung | DangerH300: Fatal if swallowed [Danger Acute toxicity, oral]H330: Fatal if inhaled [Danger Acute toxicity, inhalation]P260, P264, P270, P271, P284, P301+P316, P304+P340, P316, P320, P321, P330, P403+P233, P405, and P501 (click each P-code to see the statement) |
|---|---|
| Regulatorische Informationen | Pilocarpine: Does not have an individual approval but may be used under an appropriate group standard |
| Weitere Sicherheitsinformationen | IMAP assessments - 2(3H)-Furanone, 3-ethyldihydro-4-[(1-methyl-1H-imidazol-5-yl)methyl]-, (3S-cis)-: Human health tier I assessmentIMAP assessments - 2(3H)-Furanone, 3-ethyldihydro-4-[(1-methyl-1H-imidazol-5-yl)methyl]-, (3S-cis)-: Environment tier I assessment |
| Hazard Classes and Categories | Acute Tox. 2 (100%)Acute toxicity - category 2Acute toxicity (Oral) - Category 1Acute toxicity (Dermal) - Category 1Specific target organ toxicity - Single exposure - Category 1 (nervous system)Acute Tox. 2 * |
| Lagerbedingungen | KEEP WELL CLOSED & PROTECTED FROM LIGHT. /HCL/ |
| Treatment | Overdosage should be treated with atropine titration (0. 5 mg to 1. 0 mg given subcutaneously or intravenously) and supportive measures to maintain respiration and circulation. Epinephrine (0. 3 mg to 1. 0 mg, subcutaneously or intramuscularly) may also be of value in the presence of severe cardiovascular depression or bronchoconstriction. (L1712) |
| Hepatotoxicity | In clinical trials of pilocarpine, serum enzyme elevations were uncommon and no more frequent than with placebo. Despite, wide scale use, there have been no published reports of acute liver injury attributable to pilocarpine. |
| Unerwünschte Wirkungen | As the drug acts as a cholinergic agonist, pilocarpine may propagate muscarinic side effects, particularly when used in the oral form. The muscarinic receptors are present in nearly all major organ systems, and muscarinic medications can mediate autonomic function wherever the receptors are present. Due to the receptor's role in mediating the response of the parasympathetic nervous system, stimulation of the receptors will cause "rest and digest" functions throughout the distribution of M1-M5 receptor locations: the neuronal, cardiac, musculoskeletal, pulmonary, digestive, and urinary systems.Due to the location of the M3 receptors in blood vessels, vasodilation will occur, resulting in decreased blood pressure and flushing. When postganglionic muscarinic receptors are activated, sweating and diaphoresis can occur. Other toxicity symptoms may include miosis or excess lacrimation (especially when using the ocular form), hypersalivation, vomiting, bradycardia, bronchospasm, urination, and diarrhea. Sweating is the most common side effect in those on the oral dosage form and even more common in patients on higher doses of daily oral pilocarpine. |
| Expositionspfade | Oraleye contact. There was a decrease in the rate of absorption of pilocarpine from SALAGEN Tablets when taken with a high fat meal by 12 healthy male volunteers |
| Toxizitätsübersicht | It is essential to monitor for side effects of excessive stimulation of the muscarinic receptors, as previously due to the systemic effects of the oral preparation. Fortunately, pilocarpine is not among the narrow therapeutic index medications. However, there is no known antidote for treating these side effects, and care should still be taken by the healthcare team to monitor doses and weigh the pros and cons of treatment. If a patient is unable to tolerate the side effects of pilocarpine, they should notify their healthcare team, who may either decrease the dose or discontinue the treatment.Pilocarpine is a cholinergic parasympathomimetic agent. It increase secretion by the exocrine glands, and produces contraction of the iris sphincter muscle and ciliary muscle (when given topically to the eyes) by mainly stimulating muscarinic receptors. |
| Natural Pollution Sources | PILOCARPINE IS CHIEF ALKALOID OBTAINED FROM LEAFLETS OF SOUTH AMERICAN SHRUBS OF GENUS PILOCARPUS. ...IT WAS LONG KNOWN BY NATIVES THAT CHEWING OF LEAVES OF PILOCARPUS PLANTS CAUSED SALIVATION, 1ST EXPT WERE...PERFORMED IN 1874 BY BRAZILIAN PHYSICIAN NAME COUTINHOU.FROM PILOCARPUS JABORANDI HOLMES, RUTACEAE: PETIT, POLANOVSKI, BULL SOC CHIM (3) 17, 557, 702 (1897). |
| Human Toxicity Excerpts | LOCAL IRRITATION, ALLERGIC REACTIONS, & SYSTEMIC EFFECTS ARE UNCOMMON. 1 CASE OF MALFUNCTION IN EUSTACHIAN TUBE & DISTURBANCE IN MIDDLE EAR HAS BEEN REPORTED AFTER USE OF 4% SOLN /OF PILOCARPINE/.HAZINESS OF CORNEAL EPITHELIUM & SUPERFICIAL CORNEAL VASCULARIZATION WITH REDNESS OF CONJUNCTIVA HAVE BEEN OBSERVED...IN 2 PT AFTER LONG-CONTINUED USE OF PILOCARPINE EYEDROPS.ADVERSE SIDE EFFECTS FROM TOPICAL USE ON EYE ARE FEW, CONSISTING OF SENSATION OF DIMNESS OF VISION...ENFORCED ACCOMMODATION FOR NEAR, CAUSING PSEUDOMYOPIA & IMPROPER FOCUSING...BY PEOPLE BELOW AGE OF PRESBYOPIA. ACHING DISCOMFORT IN EYE FROM CONTRACTION OF CILIARY MUSCLE...@ START OF TREATMENT WITH...EYEDROPS.SALIVARY, LACRIMAL, GASTRIC, PANCREATIC, & INTESTINAL GLANDS, & MUCOUS CELLS OF RESP TRACT ARE...STIMULATED BY.../PILOCARPINE/. ...AFTER PILOCARPINE, COMPOSITION OF SALIVA TENDS TO APPROACH...ULTRAFILTRATE OF PLASMA. ... GASTRIC GLANDS...SECRETE JUICE...ESP ABUNDANT IN PEPSIN & MUCIN...For more Human Toxicity Excerpts (Complete) data for PILOCARPINE (12 total), please visit the HSDB record page. |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)PilocarpineAmbiguous-DILI-concern3Adverse reactionsDOI:10.1016/j.drudis.2016.02.015 |
| Non-Human Toxicity Excerpts | ALL PARASYMPATHOMIMETIC DRUGS, IN TOXIC DOSES, STIMULATE ALL SECRETIONS & PRODUCE SEVERE GI COLIC & DIARRHEA & DYSPNEAIRIS IS MARKEDLY CONSTRICTEDHEART RATE IS 1ST INCR & THEN SLOWED. DEATH MAY BE DUE TO RESP PARALYSIS OR HEART BLOCK. /PARASYMPATHOMIMETIC DRUGS/...INJECTION OF PILOCARPINE INTO CEREBRAL VENTRICLES OF...RABBIT PRODUCED VARIETY OF AUTONOMIC & SOMATIC MOTOR EFFECTS...PILOCARPINE...BEEN FOUND TO EVOKE CHARACTERISTIC CORTICAL AROUSAL OR ACTIVATION RESPONSE IN CATS FOLLOWING IV INJECTION OF RELATIVELY SMALL DOSES... |
| Antidote and Emergency Treatment | TREATMENT CONSISTS IN PARENTERAL ADMIN OF ATROPINE, & ADEQUATE MEASURES TO SUPPORT RESP & CIRCULATION & TO COUNTERACT PULMONARY EDEMA. |
| Effects During Pregnancy and Lactation | ◉ Summary of Use during LactationLimited information indicates that maternal use of ophthalmic pilocarpine did not adversely affect the breastfed infant. If ophthalmic pilocarpine is used during breastfeeding, monitor the infant for signs of cholinergic excess (diarrhea, lacrimation, and excessive salivation or urination), especially in younger, exclusively breastfed infants. To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue.Because no information is available on the use of oral pilocarpine during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.◉ Effects in Breastfed InfantsA woman with glaucoma used a pilocarpine insert (Ocusertstrength not specified) in one eye while nursing (extent not stated) her newborn infant for 9 weeks. No adverse reactions were noted in the infant.[1]A mother who was taking pilocarpine eye drops (concentration not stated) twice daily as well as 2 drops of timolol 0.5% eye drops daily and acetazolamide 250 mg orally twice daily and delivered a preterm infant at 36 weeks of gestation. The infant began 5 months of exclusive breastfeeding at 6 hours after birth. On day 2, the infant developed electrolyte abnormalities consisting of hypocalcemia, hypomagnesemia, and metabolic acidosis. The infant was treated with oral calcium gluconate and a single dose of intramuscular magnesium sulfate. Despite continued breastfeeding and maternal drug therapy, the infant's mild metabolic acidosis disappeared on day 4 of life and the infant was gaining weight normally at 1, 3 and 8 months, but had mild hypotonicity. The authors considered the metabolic effects to be caused by transplacental passage of acetazolamide that resolved despite the infant being breastfed. The infant gained weight adequately during breastfeeding, but had some mild, residual hypertonicity of the lower limbs requiring physical therapy.[2]◉ Effects on Lactation and BreastmilkRelevant published information in nursing mothers was not found as of the revision date. In animals, cholinergic drugs increase oxytocin release,[3] and have variable effects on serum prolactin.[4] Other centrally acting cholinergic drugs increase serum prolactin in humans.[5][6] The prolactin level in a mother with established lactation may not affect her ability to breastfeed. |
| Wassergefährdungsklasse (WGK) | 3 |
| TSCA-Inventar-Status | TSCA listed |
| UN-Transportnummer | 1544 |
| Zollcode | 2939800000 |
| R-Sätze (R) | 26/28 |
| Gefahrensymbole | T+ |
| Sicherheitshinweise (S) | 25-45 |
| Gefahrenklasse | 6.1(b) |
| Verpackungsgruppe | III |
| Gefahrstoffdaten | 92-13-7(Hazardous Substances Data) |
Anwendungen & Verwendung
Beschreibung
Pilocarpine acts by stimulating muscarinic receptors, therefore making it similar in action to acetylcholine when systematically introduced. This compound differs from acetylcholine in that it does not react with any nicotinic receptors, but by stimulating the CNS. Its effects are blocked by atropine. It has found therapeutic use in ophthalmology as a myotic agent.
History
It has a history of hundreds of years since pilocarpine was used to treat glaucoma .In 1933, the chemical synthesis of pilocarpine was firstly reported. However, pilocarpine couldn’t be used for treatments, because its synthetic route is so long and focuses on isopilocarpine, of which the pharmacological activities are 1/20– 1/50 of pilocarpine. In 1972, DeGraw successfully synthesized the cis-homopilopic acid employing catalytic hydrogenation of precious metals and obtained pilocarpine as the main part product. Therefore, the study on the production of pilocarpine by chemical synthesis has made new progress and has been artificially synthesized .
Verwenden
Pilocarpine occurs in the leaves of variousspecies of pilocarpus. It is used as an antidotefor atropine poisoning and in ophthalmologyto produce contraction of the pupil.