Pilocarpinae Nitras. Pilocarpine Nitrate, U.S.P.

Pilocarpus Jaborandi, Holmes, Microphyllus, Stapf. The hydrochloride and nitrate of pilocarpine,an alkaloid obtained from the dried leaflets.

Habitat. 1. Brazil -- from Pernambuco; 2, Brazil -- from Maranham; Paraguay, Uruguay; in forest-cleanings on the hill-slopes.

Syn. Pilocarp., Jaborandi, Pilocarpi Foliata; 1. Pernambuco Jaborandi. 2. Maranham Jaborandi; Fr. Jaborandi; Ger. Folia Jaborandi, Jaborandiblatter; Pilocarpin, Hydrochl., Pilocarpine Chloride, Pilocarpinae Hydrochloras; Fr. Chlorhydrate de Pilocarpine; Ger. Pilocalpinum hydrochloricum, Pilokarpin-hydrochlorid; Pilocarpin, Nit.; Fr. Azotate de Pilocarpine; Ger. Pilocarpinum nitricum, Pilokarpinnitrat.

Pi-lo-car'pus. L. pilus, hair, or fr. Gr.... a cap, + ... fruit -- i.e., fruit hat-shaped.

Jab-o-ran'di. L. fr. Port. zha-bo-ran-de' -- i.e., South American name.

Mi-cro-phyl'lus. L. fr. Gr.... small, + ... leaf -- i.e., having small leaves.

Plants

Shrubs 1.2-1.5 M. (4-5 degrees) high, branches erect; bark smooth, with gray and white dots, roots 18 Mm. (3/4') thick; flowers small, pinkish-purple, pedicellate, racemes 45 Cm. (18') long; fruit, 5 carpels 4 Cm. (1 3/5') long, compressed, curved ridges dotted with oil-glands, carpels 1-seeded, reniform, black; leaves imparipinnate, .3-.4 M. 1-1 ½ degrees long, (2-5 pairs. Leaflets (P Jaborandi): Pernambuco, oval, oblong, elliptical, 4-10.5 Cm. (1 3/5-4') long, 2-4 Cm. (4/5-1/3/5') broad, short, stout petiolules, acute, emarginate (rounded), base rounded or acute, mostly unequal, entire, narrowly revolute, smooth, shiny, coriaceous, glandular-punctate, grayish-brownish-green above, midrib mostly depressed, yellowish-, greenish-brown beneath, slightly pubescent on the prominent midvein; peculiarly aromatic when crushed; taste bitterish, becoming pungent with sialagogue effect; (P. Microphyllus): Maranham, rhomboidally oval, obovate, elliptical, 1.5-5 Cm. (3/5-2') long, 1-3 Cm. (2/5-1 1/5') broad, lateral ones nearly sessile, terminal ones on margined petiolules, .5-1.5 Cm. (1/5-3/5') long, nearly uniform grayish-, yellowish-green, rather thin, otherwise resembling the preceding. Powder, dark green-, greenish-brown -- epidermal cells 5-6 sided, stomata usually with 4 neighboring cells, fragments of fibro-vascular bundles showing tracheae, wood-fibers, bast-fibers, rosette aggregates of calcium oxalate, oil-secretion reservoirs with oil globules, non-glandular hairs; solvents: diluted alcohol; boiling water partially. Dose, gr. 15-30 (1-2 Gm.).

Adulterations

Leaves from which pilocarpine has been extracted, or leaves of Pilocarpus species possessing little activity or of piperaceous plants (thin, subcoriaceous, ovate, not emarginate but acuminate, finely granular, not pellucid-punctate), or of Monnie'ra trifo'lia and Casca'ria species, or leaflets of Swart'zia decip'iens (ovoid, short hairy petiole, upper surface shining, lower minutely hairy, not pellucid-punctate, some only 5 Mm. (1/5') long), for "Maranham Jaborandi," sometimes 30 p.c., or "False Jaborandi"--leaves of Haematoxylon campechianum, notched apex, pellucid-punctate, without alkaloid, with red-bown secreting vessels, cinnamon and clove odor.

Commercial

Plant was introduced into Europe, 1847, and now is cultivated. The names Jaborandi, Jamborandi, laborandi are applied natively, in both generic and specific sense, to several dissimilar pungent plants having sialagogic, diaphoretic and sudorific properties, as Serro'nea Jaborandi, Piper Jaborandi (possibly the true Jaborandi), P. unguicula'tum, P. citrifo'lium, P. reticula'tum, P. Mollico'mum, Erte'la (Auble'tia) trifo'lia, Xanthoxylum el'egans. Leaves should be collected when grown, after rainy season, and, inclining to mustiness, should be dried thoroughly before packing. The once official species are high-priced, scarce, and subject to much substitution, while the Rio Jaborandi (P. Selloanus), also once official and popular, continues to have a limited demand in spite of great irregularity in characteristics and constituents.

Constituents

Pilocarpine .5-1 p.c. (1874), isopilocarpine, pilocarpidine, jaborine (?), volatile oil .5 p.c., (resin, tannin, malic acid, salts), ash 7 p.c.

Pilocarpine (Pilocarpina), CHON. -- This liquid alkaloid, as first obtained under the name of jaborandine, was believed to be volatile, but this is not true, although it occurs as a colorless, syrupy liquid.  It may be prepared by moistening powdered leaves with solution of sodium carbonate, exhausting with warm benzene, shaking out with diluted hydrochloric acid, after separation rendering acid solution alkaline with solution of sodium carbonate, shaking out with chloroform, evaporating chloroformic liquid getting residue of crude alkaloids; neutralize with diluted nitric acid, evaporate to dryness, purify by repeated crystallization from alcohol, dissolve pilocarpine nitrate in water, render alkaline with ammonia, shake out with chloroform, evaporate getting pure pilocarpine as a colorless syrupy liquid; it is soluble in water, alcohol, chloroform, slightly in ether, forms crystallizable salts (hydrochloride, nitrate, etac.); resembles nicotine in action.

Pilocarpinae Hydrochloridum. Pilocarpine Hydrochloride, CHON.HCl. -- Obtained by neutralizing diluted hydrochloric acid (17.5) with pilocarpine (10), concentrating, setting aside over sulphuric acid to crystallize; it is in colorless, translucent crystals, odorless, faintly bitter taste, hygroscopic on exposure, soluble in water (.3), alcohol (3), hot alcohol (1.5), chloroform (366), insoluble in ether; aqueous solution (1 in 20) slightly acid, melts at 197 degrees C. (387 degrees F.).  Tests: 1. To aqueous solution (.01-.02 in 2) add 2 cc.acid hydrogen dioxide T.S., benzene layer -- violet, aqueous layer -- yellow (dist. from other alkaloids).  2. Aqueous solution with silver nitrate T.S. -- white precipitate, insoluble in nitric acid.  3. Solution of .1 Gm. in 2 cc. sulphuric acid -- colorless or faintly yellow (abs. of readily carbonizable substances).  4. Add to 10 cc. aqueous solution (1 in 100) ammonia T.S., or potassium dichromate T.S. -- no turbidity (abs. of foreign alkaloids); ash from .1 Gm. -- negligible.  Impurities: Foreign alkaloids, readily carbonizable substances.  Should be kept dark, in well-closed containers.  Dose, gr. 1//8-1/2 (.008-.03 Gm.), administered best hypodermically (2 p.c. aqueous solution.).

Pilocarpinae Nitras. Pilocarpine Nitrate, CHONHNO. -- Obtained by neutralizing diluted nitric acid (121) with pilocarpine (40), evaporating to dryness, redissolving in alcohol, crystallizing; it is in shining crystals, odorless, permanent, soluble in water (4), alcohol (75), hot alcohol (21), insoluble in chloroform, ether, melts at 172 degrees C. (342 degrees F.).  Tests: 1. Aqueous solution mixed with equal volume of ferrous sulphate T.S. and carefully poured over sulphuric acid without shaking -- brown ring at juncture of two layers.  2. To 5 cc. aqueous solution (1 in 50), acidulated with nitric acid, + few drops silver nitrate T.S.-no immediate opalescence (abs. of chloride); ash from .1 Gm. -- negligible.  Impurities: Chloride, etc.  Should be kept dark, in well-closed containers.  Dose, gr. 1/8-1/2 (.008-.03 Gm.), administered best hypodermically (2 p.c. aqueous solution).

Isopilocarpine. -- Obtained by action of heat or alkali on pilocarpine; it is a colorless, viscid oil, oxidizing into pilocarpic acid, CHON, boiling at 261 degrees C. (502 degrees F.), distilling without decomposition, isomeric with pilocarpine; pilocarpidine, CHON, found in P. Jaborandi but not in P. Microphyllus, is a liquid body, differing from pilocarpine by auric chloride not precipitating aqueous solutions, in being weaker, deliquescent, oxidizing in air to syrupy jaboridine (possibly identical with jaborandine, CHON; jaborine, CHON, is of doubtful occurrence, although formerly believed to be in the leaves and to be formed by evaporating acid solutions of pilocarpine; as such it was yellow, amorphous, less soluble in water, but more so in ether than pilocarpine, isomeric with it (same molecular formula), but antagonizing its action, resembling atropine; the commercial jaborine has been found to be a brown oil composed of isopilocarpine, pilocarpidine, pilocarpine, and coloring matter.

Volatile Oil. -- Obtained by distillation at 176 degrees C. (350 degrees F.), and is chiefly a terpene pilocarpene) CH, with little solid paraffin-like substance, sp. gr. 0.875.

Preparations

(Unoff.).  LEAVES: Fluidextract (67 p.c. alcohol), dose, mxv-30 (1-2 cc.).  Extract, gr. 3-10 (.2-.6 Gm.).  Infusion, 3j-2 (30-60 cc.).  Tinctura Pilocarpi (Jaborandi), 20 p.c., 3ss-2 (2-8 cc.).  Pilocarpine, phosphate, acetate, hydrobromide, dose, each gr. 1/8-1/2 (.008-.03 Gm.), hypodermically.

Properties

Diaphoretic, sialagogue, myotic, cardiac depressant, emetic, diuretic (repeated small doses), galactagogue, abortive.  Full doses cause flushed face, quickened circulation and respiration, profuse sweating and salivation (lasting 2-4 hours, losing in perspiration 9-15ounces (.27-.45 L.), in saliva 10-27 ounces (.3-.8 L.), these always being in the inverse ratio); increases bronchial, nasal, mammary, gastric, and intestinal secretions, lowers temperature 1-4 degrees, contracts pupils, produces chilliness and weakness.  The heart soon becomes slowed and arterial pressure lowered, by stimulating the terminations of the vagus, or by depressing the motor centers in the heart-muscle.  Both the fluid and solids (especially urea) of the perspiration are increased by direct influence on the nerve-endings govening its secretion, while the cells of the salivary glands are stimulated directly.   Pilocarpine produces identical effects of the drug; isopilocarpine is 8-10 times weaker than pilocarpine, while jaborine irritates the stomach, causing nausea, vomiting, etc.

Uses

Dropsies, pleurisy, uremia, pulmonic edema, catarrhal jaundice, mumps, rheumatism, coryza, cold, influenza.  Bright's disease, menengitis, diabetes, agalactia, parotitis, asthma, hiccough, erysipilas, diphtheria; best antidote to atropine, hyoscyamine, daturine, agaricin, etc.; powerful stimulant to hair growth -- locally and internally.  In ophthalmia use pilocarpine, in amblyopia (from alcohol or tobacco), detached retina, chronic iritis, keratitis, glaucoma, atrophic choroiditis, instead of physostigmine as a myositic.  To avoid nausea, may give in form of enema.

Poisoning

Have profuse sweating, dizziness, salivation, vomiting, purging, contracted pupils, pain in eyes.  Empty the stomach and wash it out with tannin; give atropine hypodermically and morphine to control nausea and vomiting; cardiac stimulants if necessary.

Incompatibles

Atropine, agaricin, morphine, tannin, caustic alkalies, ferric and metallic salts.

Synergists

Aconite, veratrum viride, gelsemium, sarsaparilla, spirit of ethyl nitrite, and drugs which paralyze the vasomotor system.  P. Selloa'nus (possibly the same as P. Pinnatifo'lius, leaflets under both names formerly official); P. Grandiflo'rus, P. Pauciflo'rus, P. Heterophy'lus, P. Spica'tus, P. Trachylo'phus -- all have similar medicinal value.