(±)-Atropine

289.37

289.37

200-104-8

DTXSID4020113

Long, orthorhombic prisms from acetone|Rhombic needles (dilute ethyl alcohol)|White crystals or powder

A - Alimentary tract and metabolism

29399900

49.8

1.83

white powder

1.2±0.1 g/cm3

118.5 °C

429.8±45.0 °C at 760 mmHg

2℃

1.581

1.6g/L(18 ºC)

-20°C

Oral-rat LD50: 500 mg/kg; Oral-Mouse LD50: 75 mg/kg

Combustible; burning produces toxic nitrogen oxide fumes; patient side effects of medication; visual changes; pupil dilation, muscle weakness

pH of 0.0015 molar soln: 10.0

pKa = 4.35|pKa = 9.43

Sublimes in high vacuum at 93-110 °C|Granules or powder, mp 190-194 °C. Almost inactive optically. Very bitter. pH approx 5.4. One gram dissolves in 0.4 mL water; 5 mL cold, 2.5 mL boil. alc; in 2.5 mL glycerol, 420 mL chloroform, 3000 mL ether. ... Incompatible with alkalies, tannin, salts of mercury or gold, vegetable decoctions or infusions, borax, bromides, iodides, benzoates. /Sulfate monohydrate/

6.1

1544

3

26/28-36/37/38-20/21/22-36-11

25-45-36-26-36/37-16

CK0700000

T+,Xn,F

Ventilated, low temperature and dry; stored separately from food materials in warehouse

Atropine sulfate should be stored below 40 deg C, preferably at room temp. Freezing should be avoided. Minimum hydrolysis occurs at pH 3.5. Atropine sulfate 1 mg/ml was found to retain potency for 3 months at room temp when 0.5 or 1 ml of soln was packaged in Tubex. /Atropine sulfate/

P210-P261-P305 + P351 + P338-P311

H225-H302-H319-H331

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl atropine sulfate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Atropine sulfate/|Schedules of controlled substances are established by section 202 of the Controlled Substances Act (21 U.S.C. 812). Schedule IV includes: not more than 1 mg of difenoxin and not less than 25 ug of atropine sulfate per dosage unit, DEA Code #9167; Drug class: narcotic drugs.|Schedules of controlled substances are established by section 202 of the Controlled Substances Act (21 U.S.C. 812). Schedule V includes: not more than 2.5 mg of diphenoxylate and not less than 25 ug of atropine sulfate per dosage unit; Drug class: narcotic drugs containing non-narcotic active medicinal ingredients.|Schedules of controlled substances are established by section 202 of the Controlled Substances Act (21 U.S.C. 812). Schedule V includes: not more than 0.5 mg of difenoxin and not less than 25 ug of atropine sulfate per dosage unit; Drug class: narcotic drugs containing non-narcotic active medicinal ingredients.

|Danger|H300: Fatal if swallowed [Danger Acute toxicity, oral]|P260, P264, P270, P271, P284, P301+P310, P304+P340, P310, P320, P321, P330, P403+P233, P405, and P501|H300 (71.35%): Fatal if swallowed [Danger Acute toxicity, oral]|P260, P262, P264, P270, P271, P280, P284, P301+P310, P302+P350, P304+P340, P310, P320, P321, P322, P330, P361, P363, P403+P233, P405, and P501|Aggregated GHS information provided by 185 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]|Aggregated GHS information provided by 43 companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H302: Harmful if swallowed [Warning Acute toxicity, oral]|P260, P264, P270, P301+P312, P307+P311, P321, P330, P405, and P501

SLIGHT.

highly toxic

Despite widespread use over many decades, atropine has not been linked convincingly to episodes of liver enzyme elevations or clinically apparent liver injury. Atropine is metabolized by the liver, but is usually given in low doses (|Despite widespread use over many decades, hyoscyamine has not been linked to episodes of liver enzyme elevations or clinically apparent liver injury. A major reason for its safety may relate to the low daily dose and limited duration of use.

...INTENSIFY EFFECTS OF ATROPINE. ALUMINUM-CONTAINING ANTACIDS & MAGNESIUM TRISILICATE PROBABLY INTERFERE WITH ABSORPTION...|ACTION OF ATROPINE POTENTIATES & IS POTENTIATED BY OTHER ANTICHOLINERGICS, SYMPATHOMIMETICS, CHOLINOLYTICS, MUSCARINIC RECEPTOR ANTAGONISTS. ACTION OF ATROPINE ANTAGONIZES & IS ANTAGONIZED BY CHOLINERGIC AGENTS, ANTICHOLINESTERASES, MUSCARINIC RECEPTOR AGONISTS, PARASYMPATHOMIMETICS, SYMPATHOLYTICS.|ATROPINE MAY ANTAGONIZE CNS DEPRESSANT DRUGS & POTENTIATE CNS EXCITATORY DRUGS. MAY EITHER POTENTIATE OR ANTAGONIZE TRANQUILIZERS.|/Atropine and Succinylcholine/. This combination though commonly used in children has been observed to incr the occurrence of skeletal muscle rigidity with malignant hyperthermia.|For more Interactions (Complete) data for ATROPINE (10 total), please visit the HSDB record page.

LD50 Rat oral 500 mg/kg|LD50 Rat ip 280 mg/kg|LD50 Rat sc 250 mg/kg|LD50 Rat iv 73 mg/kg|For more Non-Human Toxicity Values (Complete) data for ATROPINE (9 total), please visit the HSDB record page.

/BIRDS and MAMMALS/ Atropine, an anticholinergic agent commonly used in human and veterinary medicine, is reported to cause toxicity associated with its antimuscarinic action. A juvenile pygmy sperm whale, Kogia breviceps, was treated with atropine in an attempt to relieve symptoms similar to pyloric stenosis, as has been used in humans. Two doses of 0.01 mg/kg were given im, 12 hr apart, followed by three doses of 0.005 mg/kg im sid over the next 3 days. Symptoms associated with atropine toxicity developed gradually and included hyperexcitability, a generalized ascending paralysis of body musculature, shallow, rapid respiration, vomiting, aspiration of seawater, and pulmonary edema. Treatment with physostigmine salicylate (two doses of 2 mg im, I hr apart) was effective in counteracting the paralysis, as well as other symptoms, beginning in as little as 17 min after the first dose, and the whale was back to swimming on its own after 8 hr. All overt symptoms of atropine toxicity were gone in about 24 hr, but there were other possible sequella that lasted much longer.

...From Atropa belladonna L., Datura stramonium L., and other Solanaceae.|...ATROPINE HAS NOT BEEN SHOWN TO OCCUR IN NATURAL SOURCES AS ALKALOID; IT IS RACEMIC MIXT OF D- & L-HYOSCYAMINE...|Jimson weed (Datura stramonium) and the deadly nightshade (Atropa belladonna) contain the alkaloids atropine, hyoscyamine, and hyoscine(1). These alkaloids also are found in other plants belonging to the Solanaceae family and in toxic amounts(1).

Atropine is a natural alkaloid anticholinergic agent that has potent antimuscarinic effects and is used by injection to treat symptomatic bradycardia, severe bronchospasm and to reduce vagal stimulation. Atropine has not been implicated in causing liver enzyme elevations or clinically apparent acute liver injury.|Hyoscyamine as a natural plant alkaloid derivative and anticholinergic that is used to treat mild to moderate nausea, motion sickness, hyperactive bladder and allergic rhinitis. Hyoscyamine has not been implicated in causing liver enzyme elevations or clinically apparent acute liver injury.

Anticholinergic Agents|Gastrointestinal Agents

Adjuvants, Anesthesia; Anti-Arrhythmia Agents; Antidotes; Bronchodilator Agents; Muscarinic Antagonists; Mydriatics; Parasympatholytics|... people poisoned by anticholinesterase organic phosphorus compounds have an increased tolerance for atropine sulfate.|MEDICATION (VET): ...USED ROUTINELY AS ADJUNCT TO GENERAL ANESTHESIA...TO DECR SALIVARY & AIRWAY SECRETIONS. ... USED TO FACILITATE OPHTHALMOSCOPIC EXAM OF INTERNAL OCULAR STRUCTURES & FUNCTIONS &...FOR TREATMENT OF VARIOUS OCULAR DISORDERS. ... ATROPINE IS ESSENTIAL ANTIDOTE TO ANTICHOLINESTERASE OVERDOSAGE & POISONING.|Adequate doses of atropine can abolish many types of reflex vagal cardiac slowing or asystole--for example, from inhalation of irritant vapors, stimulation of the carotid sinus, pressure on the eyeballs, peritoneal stimulation, or injection of contrast dye during cardiac catheterization. It also prevents or abruptly abolishes bradycardia or asystole caused by choline esters, acetylcholinesterase inhibitors, or other parasympathomimetic drugs, as well as cardiac arrest from electrical stimulation of the vagus.|For more Therapeutic Uses (Complete) data for ATROPINE (24 total), please visit the HSDB record page.

FATALITIES FROM ATROPINE...ARE RARE, BUT SOMETIMES OCCUR IN CHILDREN. OF ALL POTENT ALKALOIDS, ATROPINE HAS ONE OF WIDEST MARGINS OF SAFETY. FATAL DOSE... NOT KNOWN; 200-MG DOSE..USED THERAPEUTICALLY FOR MENTAL ILLNESS, &...1000 MG HAVE BEEN SURVIVED. IN CHILDREN, 10 MG OR LESS MAY BE LETHAL.|DRY MOUTH, BLURRED VISION, PHOTOPHOBIA, ANHIDROSIS, & CONSTIPATION ARE UNAVOIDABLE SIDE EFFECTS...|...CONTRAINDICATED IN PERSONS WHOSE INTRAOCULAR PRESSURE IS...ELEVATED...IN PRESENCE OF PROSTATIC HYPERTROPHY OR ORGANIC PYLORIC STENOSIS. ...USED CAUTIOUSLY IN PT WITH PROSTATISM, URINARY RETENTION, DIABETES, HYPERTHYROIDISM, TACHYCARDIA, IN ELDERLY PERSONS, & CHILDREN UNDER 6 YR OF AGE.|ATROPINE IS OF NO VALUE IN DELAYED TYPE OF MUSHROOM POISONING DUE TO TOXINS OF A PHALLOIDES & CERTAIN OTHER SPECIES OF SAME GENUS.|For more Drug Warnings (Complete) data for ATROPINE (16 total), please visit the HSDB record page.

TOLERANCE TO BELLADONNA DRUGS OCCURS...TO LIMITED EXTENT. HABITUATION & ADDICTION DO NOT OCCUR...

Agents that inhibit the actions of the parasympathetic nervous system. The major group of drugs used therapeutically for this purpose is the MUSCARINIC ANTAGONISTS. (See all compounds classified as Parasympatholytics.)|Agents that are administered in association with anesthetics to increase effectiveness, improve delivery, or decrease required dosage. (See all compounds classified as Adjuvants, Anesthesia.)|Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade. (See all compounds classified as Anti-Arrhythmia Agents.)|Agents that cause an increase in the expansion of a bronchus or bronchial tubes. (See all compounds classified as Bronchodilator Agents.)|Agents that dilate the pupil. They may be either sympathomimetics or parasympatholytics. (See all compounds classified as Mydriatics.)|Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system. (See all compounds classified as Muscarinic Antagonists.)

BELLADONNA ALKALOIDS...ARE ABSORBED RAPIDLY FROM THE GI TRACT. THEY ALSO ENTER CIRCULATION WHEN APPLIED...TO MUCOSAL SURFACES OF THE BODY. ABSORPTION FROM INTACT SKIN IS LIMITED, ALTHOUGH EFFICIENT ABSORPTION DOES OCCUR IN THE POSTAURICULAR REGION. ... ATROPINE HAS A HALF-LIFE OF APPROX 4 HR; HEPATIC METAB ACCOUNTS FOR THE ELIMINATION OF ABOUT HALF OF A DOSE, & THE REMAINDER IS EXCRETED UNCHANGED IN THE URINE.|...WHEN ADMIN TO MOTHER PASS RAPIDLY INTO FETAL BLOOD.|IN DOG, 27% OF SC DOSE OF (3)H-ATROPINE WAS EXCRETED IN 2-HR URINE MOSTLY UNCHANGED. 50%...WAS EXCRETED WITHIN 6-HR, & RENAL EXCRETION OF ATROPINE OCCURRED BY GLOMERULAR FILTRATION & TUBULAR SECRETION.|AFTER IM ADMIN OF RADIOACTIVELY LABELED ATROPINE TO MAN, DISAPPEARANCE OF RADIOACTIVITY FROM PLASMA WAS BIPHASIC, WITH...HALF-LIVES OF 2 HR & 13-28 HR... BETWEEN 77 & 94% OF TOTAL RADIOACTIVITY WAS EXCRETED IN URINE... CHROMATOGRAPHIC EVIDENCE SUGGESTED THAT RELATIVE PROPORTIONS OF METABOLITIES VARIED WITH TIME.|For more Absorption, Distribution and Excretion (Complete) data for ATROPINE (6 total), please visit the HSDB record page.

... HEPATIC METAB ACCOUNTS FOR THE ELIMINATION OF ABOUT HALF OF A DOSE, & THE REMAINDER IS EXCRETED UNCHANGED IN THE URINE.|WITH (14)C RESTRICTED TO ALPHA-CARBON...ON TROPIC ACID PORTION...10 RADIOACTIVE...PRODUCTS...IN MOUSE & RAT URINE, PRINCIPAL METABOLITES WERE GLUCURONIDE CONJUGATES OF HYDROXYATROPINES FORMED IN VIVO BY METABOLIC HYDROXYLATION OF AROMATIC RING...GLUCURONIDES OF ATROPINE COULD NOT BE DETECTED IN HUMAN URINE...

AFTER IM ADMIN OF RADIOACTIVELY LABELED ATROPINE TO MAN, DISAPPEARANCE OF RADIOACTIVITY FROM PLASMA WAS BIPHASIC, WITH...HALF-LIVES OF 2 HR & 13-28 HR...

Atropine... competes with ACh & other muscarinic agonists for a common binding site on the muscarinic receptor. The binding site for competitive antagonists & acetylcholine is in a cleft predicted to be formed by several of the receptor's 7 transmembrane helices, as shown recently for the position of retinol in the mammalian rhodopsin structure. An aspartic acid present in the N-terminal portion of the third transmembrane helix of all 5 muscarinic receptor subtypes is believed to form an ionic bond with the cationic quaternary nitrogen in acetylcholine & the tertiary or quaternary nitrogen of the antagonists.|ATROPINE...(IS A) SELECTIVE ANTAGONIST OF MUSCARINIC AGENTS AT CORRESPONDING RECEPTORS OF SMOOTH & CARDIAC MUSCLE & EXOCRINE GLAND CELLS. THIS ANTAGONISM IS SO SELECTIVE THAT ATROPINE BLOCKADE OF ACTIONS OF NONCHOLINOMIMETIC DRUG... TAKEN AS EVIDENCE THAT DRUG ACTS INDIRECTLY THROUGH ACH RELEASE OR SOME OTHER CHOLINERGIC MECHANISM.|...The site of action of atropine, a non-selective muscarinic receptor antagonist, in reducing increased muscle rigidity ...induced by the selective dopamine D2 receptor antagonist, raclopride /was investigated/. Atropine significantly reduced raclopride-induced EMG increases in rat hindlimb muscles, when injected into the ventral striatum, but not the dorsal striatum or the substantia nigra. Atropine's site of action was localized to a small area of muscarinic receptors within the ventral part of the striatum... These findings provide new information about the regulation of motor control by muscarinic receptor antagonists & additional evidence about the functional heterogeneity of the striatum.

Measures to limit intestinal absorption should be initiated without delay if the poison has been taken orally. For symptomatic treatment, slow iv injection of physostigmine rapidly abolishes the delirium & coma caused by large doses of atropine but carries some risk of overdose in mild atropine intoxication. Since physostigmine is metabolized rapidly, the patient may again lapse into coma within 1-2 hr, & repeated doses may be needed.|If marked excitement is present & more specific treatment is not available, a benzodiazepine is the most suitable agent for sedation & for control of convulsions. Phenothiazines or agents with antimuscarinic activity should not be used, because their antimuscarinic action is likely to intensify toxicity. Support of respiration & control of hyperthermia may be necessary.|VET: IF POISONING IS DUE TO INGESTION OF PLANT...WASH OUT STOMACH &...INDUCE EMESIS IF POSSIBLE. STIMULANTS MAY ALSO BE GIVEN, BUT...CHOLINERGIC DRUGS (PILOCARPINE, PHYSOSTIGMINE) AS...ANTAGONISTS MAY BE...HARMFUL...SINCE THEY WILL FURTHER DEPRESS RESP. ...ANIMALS SHOULD BE KEPT MOVING IN EARLY STAGES.

/HUMAN EXPOSURE STUDIES/ Atropine in toxic amounts leads to drowsiness, stupor, convulsions, & coma. A fatal dose may be as low as 1.6 mg & as high as 100 mg in children. Recovery in an adult has followed ingestion of 1 g. /It was/ observed that 175 ug/mg/kg (12.15 mg intramuscularly) produced initial peripheral autonomic effects such as tachycardia & dryness of mouth. Concomitant with these effects were central disturbances: somnolence, restlessness, ataxia, incoordination, hyperreflexia, hyperthermia & hypertension, disruption of awareness, & incoherent speech or inability to carry out instructions lasting 10-12 hr. Atropine sulfate 0.5 mg via nebulizer every 4 hr led to central anticholinergic intoxication; the patient recovered.|/HUMAN EXPOSURE STUDIES/ In school children, application of atropine eyedrops daily for nearly 5 yr has had no adverse effect on intraocular pressure, & no other injurious effects.|/SIGNS AND SYMPTOMS/ Seizures without prior evidence of hallucinations or delirium have followed the use of atropine in an adult & in children.|/SIGNS AND SYMPTOMS/ Atropine has been used as a premedication in obstetric anesthesia, as a test of fetoplacental insufficiency, & in the diagnosis of fetal asphyxia (atropine given to the mother produces changes in the fetal heart rate: first bradycardia, then tachycardia.) There is evidence of rapid placental transfer of atropine.|For more Human Toxicity Excerpts (Complete) data for ATROPINE (13 total), please visit the HSDB record page.

Anaspaz

BELLADONNA TINCTURE, USP...PREPN...OF AQ-ALCOHOLIC EXTRACT OF...LEAVES. ... BELLADONNA EXTRACT, NF...IN PILLS OR CAPSULES...15 MG, EQUIV TO APPROX 0.2 MG OF ATROPINE. BELLADONNA LEAF, USP...USED FOR PREPN OF TINCTURE & EXTRACT. ATROPINE, NF, IS MAIN ALKALOID OF BELLADONNA AS FREE BASE.|Dosage Forms-Injection: 0.8 mg/0.5 ml; 0.3, 0.4, 0.5, & 1.2 mg/1 ml; 0.25, 0.5 & 2.5 mg/5 ml; 4 & 10 mg/10 mgl; 8 mg/20 ml; 15 mg/30 ml;. Ophthalmic Ointment: 0.5 & 1%. Ophthalmic Solution: 0.5, 1, 2, & 3%. Tablets: 0.4 & 0.6 mg. /Atropine sulfate/|Grade: Technical, NF|ATROPINE IS USUALLY EMPLOYED IN FORM OF ITS SULFATE SALT.

Benzeneacetic acid, .alpha.-(hydroxymethyl)-, (3-endo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl ester, (.alpha.S)-: INACTIVE|Benzeneacetic acid, .alpha.-(hydroxymethyl)- (3-endo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl ester: ACTIVE|Benzeneacetic acid, .alpha.-(hydroxymethyl)-, (3-endo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl ester, (.alpha.S)-, sulfate (2:1): INACTIVE|...ATROPINE HAS NOT BEEN SHOWN TO OCCUR IN NATURAL SOURCES AS ALKALOID; IT IS RACEMIC MIXT OF D- & L-HYOSCYAMINE...|...ATROPINE MOLECULE CONSISTS OF 2 COMPONENTS JOINED THROUGH ESTER LINKAGE...ATROPINE, AN ORG BASE, &...TROPIC ACID.|Still one of the most important parasympatholytic agents.

Analyte: atropine sulfate; matrix: pharmaceutical preparation (tablet); procedure: gas chromatography with flame ionization detection (assay purity) /atropine sulfate/|Analyte: atropine sulfate; matrix: pharmaceutical preparation (tablet); procedure: infrared absorption spectrophotometry with comparison to standards or visual reaction (precipitate) (chemical identification) /atropine sulfate/|Analyte: atropine sulfate; matrix: pharmaceutical preparation (ophthalmic solution); procedure: gas chromatography with flame ionization detection (assay purity) /atropine sulfate/|Analyte: atropine sulfate; matrix: pharmaceutical preparation (ophthalmic solution); procedure: infrared absorption spectrophotometry with comparison to standards or visual reaction (precipitate) (chemical identification) /atropine sulfate/|For more Analytic Laboratory Methods (Complete) data for ATROPINE (15 total), please visit the HSDB record page.

A gas-chromatography-mass spectrometry method for the rapid quantitation of atropine in blood has a limit of detection of atropine to about 10 ng/ml.|A DROP OF URINE...FROM PT SUSPECTED OF ATROPINE TOXICOSIS CAUSES MYDRIASIS WHEN PLACED IN EYE OF CAT. ...TESTED PUPIL WILL NOT CONSTRICT WHEN EXPOSED TO LIGHT... THIS SIMPLE PROCEDURE...HELPFUL IN DIFERENTIAL DIAGNOSIS OF BELLADONNA INTOXICATION.