7424. Pilocarpine

Nomenclature

CAS number: 92-13-7
(3S-cis)-3-Ethyldihydro-4-[(1-methyl-1H-imidazol-5-yl)methyl]-2(3H)-furanone; Ocusert Pilo (Cusi).
C11H16N2O2; mol wt 208.26.
C 63.44%, H 7.74%, N 13.45%, O 15.36%.

Description and references

Cholinergic principle from Pilocarpus jaborandi Holmes, Rutaceae. Isoln: Petit, Polanovski, Bull. Soc. Chim. [3] 17, 557, 702 (1897). Structure: Jowett, J. Chem. Soc. 77, 473, 851 (1900); 83, 438 (1903). Stereoisomeric with isopilocarpine: Polonovski, Polonovski, Bull. Soc. Chim. [4] 31, 1314 (1922). Has the cis configuration; isopilocarpine is trans: Zav'yalov, Dokl. Akad. Nauk SSSR 82, 257 (1952). Absolute configuration: Hill, Barcza, Tetrahedron 22, 2889 (1966). Synthesis: Preobrashenski et al., Ber. 66, 1187 (1933); Samokhvalov, Med. Prom. SSSR 11, no. 2, 10 (1957); DeGraw, Tetrahedron 28, 967 (1972); Link, Bernauer, Helv. Chim. Acta 55, 1053 (1972). Stereoselective synthesis: A. Noordam et al., Rec. Trav. Chim. 98, 467 (1979). Review: Langenbeck, Angew. Chem. 60, 297 (1948); van Rossum et al., Experientia 16, 373 (1960). Toxicity studies: Beccari, Boll. Chim. Farm. 106, 8 (1967). Comprehensive description: A. A. Al-Badr, H. Y. Aboul-Enein, Anal. Profiles Drug Subs. 12, 385-432 (1983). Clinical trial in Sj"ogren's syndrome: F. B. Vivino et al., Arch. Intern. Med. 159, 174 (1999); in radiation-induced xerostomia: J.-C. Horiot et al., Radiother. Oncol. 55, 233 (2000).

Chemical structure

Properties

Oil or crystals, mp 34°. bp5 260° (partial conversion to isopilocarpine). [α]D18 +106° (c = 2). pK1 (20°) 7.15; pK2 (20°) 12.57. Sol in water, alcohol, chloroform; sparingly sol in ether, benzene. Almost insol in petr ether.

Derivative

Hydrochloride.

Nomenclature

CAS number: 54-71-7
Akarpine (Akorn); Almocarpine (Ayerst); Isopto Carpine (Alcon); Pilogel (Alcon); Pilopine HS (Alcon); Pilostat (Bausch & Lomb); Salagen (MGI).
C11H16N2O2.HCl; mol wt 244.72.
C 53.99%, H 7.00%, N 11.45%, O 13.08%, Cl 14.49%.

Properties

Hygroscopic crystals from alcohol, mp 204-205°. [α]D18 +91° (c = 2). Freely sol in water, alcohol. Practically insol in ether, chloroform. Keep well closed and protected from light.

Derivative

Nitrate.

Nomenclature

CAS number: 148-72-1
Chibro Pilocarpine (Chibret); Licarpin (Allergan); Pilo (Novopharma); Pilofrin (Allergan); Pilagan (Allergan).
C11H16N2O2.HNO3; mol wt 271.27.
C 48.70%, H 6.32%, N 15.49%, O 29.49%.

Properties

mp 173.5-174.0° (dec). Poisonous. [α]D +77 to +83° (c = 10). One gram dissolves in 4 ml water, 75 ml alcohol. Insol in chloroform, ether. Incompat. Silver nitrate, mercury bichloride, iodides, gold salts, tannin, calomel, KMnO4, alkalies.

Derivative

Isopilocarpine.

Nomenclature

β-Pilocarpine.

Properties

Hygroscopic oily liquid or prisms. bp10 261°. [α]D18 +50° (c = 2). pK1 (18°) 7.17. Miscible with water and alcohol; very sol in chloroform; less sol in benzene, ether. Almost insol in petr ether.

Derivative

Isopilocarpine hydrochloride hemihydrate.
C11H16N2O2.HCl. 1/2 H2O; mol wt 253.73.
C 52.07%, H 7.15%, N 11.04%, O 15.76%, Cl 13.97%.

Properties

Scales from alcohol + ether, mp 127°; when anhydr, mp 161°. [α]D18 +39° (c = 5). Sol in 0.27 part water; 2.1 parts alcohol.

Derivative

Isopilocarpine nitrate.
C11H16N2O2.HNO3; mol wt 271.27.
C 48.70%, H 6.32%, N 15.49%, O 29.49%.

Properties

Prisms from water, scales from alcohol, mp 159°. [α]D18 +39° (c = 2). Sol in 8.4 parts water, in 350 parts abs alcohol.

Therapeutic Category

Antiglaucoma agent; miotic; sialogogue.

Therapeutic Category (Veterinary)

Parasympathomimetic; miotic; gastric secretory stimulant.

Keywords

Antiglaucoma; Miotic; Sialagogue