α-adrenergic receptor[1]; (-)-Scopolamine (Atroscine) acts on α1 - adrenergic receptor and muscarinic cholinergic receptor, with Ki values of 33 μM and 7.25 nM respectively [1]

Absorption, Distribution and Excretion
The pharmacokinetics of scopolamine differ significantly across routes of administration. In healthy volunteers, after oral administration of 0.5 mg scopolamine, the peak plasma concentration (Cmax) was 0.54 ± 0.1 ng/mL, the time to peak concentration (tmax) was 23.5 ± 8.2 min, and the area under the curve (AUC) was 50.8 ± 1.76 ngmin/mL; the absolute bioavailability was low, only 13 ± 1%, likely due to first-pass metabolism. In contrast, after intravenous infusion of 0.5 mg scopolamine, 15 minutes later, the peak plasma concentration (Cmax) was 5.00 ± 0.43 ng/mL, the time to peak concentration (tmax) was 5.0 min, and the AUC was 369.4 ± 2.2 ngmin/mL. Other dosage forms have also been tested. Following subcutaneous injection of 0.4 mg scopolamine, the peak plasma concentration (Cmax) was 3.27 ng/mL, the time to peak concentration (tmax) was 14.6 min, and the area under the curve (AUC) was 158.2 ngmin/mL. Following intramuscular injection of 0.5 mg scopolamine, the peak plasma concentration (Cmax) was 0.96 ± 0.17 ng/mL, the time to peak concentration (tmax) was 18.5 ± 4.7 min, and the AUC was 81.3 ± 11.2 ngmin/mL. Intranasal administration resulted in rapid absorption; after 0.4 mg scopolamine, the peak plasma concentration (Cmax) was 1.68 ± 0.23 ng/mL, the time to peak concentration (tmax) was 2.2 ± 3 min, and the AUC was 167 ± 20 ngmin/mL. The bioavailability of scopolamine administered intranasally was also higher than that of oral scopolamine, at 83 ± 10%. Due to dose-dependent adverse reactions, a transdermal patch was developed to achieve therapeutic plasma concentrations over a longer period. Following patch application, scopolamine was detectable within 4 hours and reached peak concentration (tmax) within 24 hours. The mean plasma concentration was 87 pg/mL, and the total concentration of free and bound scopolamine reached 354 pg/mL. Following oral administration, approximately 2.6% of the unchanged scopolamine was excreted in the urine. In contrast, using the transdermal patch system, less than 10% of the total dose excreted in the urine over 108 hours (including unchanged scopolamine and its metabolites) was excreted. The amount of unchanged drug excreted was less than 5%. The volume of distribution of scopolamine has not been adequately characterized. The volume of distribution of 0.5 mg scopolamine administered intravenously was 141.3 ± 1.6 L 15 minutes later. The clearance rate of 0.5 mg scopolamine administered intravenously was 81.2 ± 1.55 L/h, while the clearance rate after subcutaneous injection was lower, at 0.14–0.17 L/h. Scopolamine hydrobromide is rapidly absorbed after intramuscular or subcutaneous injection. The drug is well absorbed in the gastrointestinal tract, primarily via the upper small intestine. Scopolamine can also be absorbed transdermally. After transdermal administration, scopolamine can be detected in plasma within 4 hours after applying a transdermal patch behind the ear, reaching peak concentrations on average within 24 hours. In a study of healthy individuals, the mean plasma concentrations of free and total (free plus bound) scopolamine were 87 pg/mL and 354 pg/mL, respectively, within 24 hours following a single topical application of the transdermal patch (releasing approximately 1 mg over 72 hours). /Scolophonamine hydrobromide/
In one subject, a peak concentration of approximately 2 ng/mL was reached within 1 hour after oral administration of 0.906 mg of scopolamine. Although commercially available transdermal patches contain 1.5 mg of scopolamine, this membrane-controlled diffusion system is designed to deliver approximately 1 mg of the drug into systemic circulation at a nearly constant rate over 72 hours. The initial dose of 0.14 mg of scopolamine is released from the system's adhesive layer at a controlled, gradually decreasing rate over 6 hours; subsequently, the remaining dose is released at a rate of approximately 5 μg/hour until the end of the system's remaining 66-hour effective duration. The manufacturer states that the initial starting dose saturates binding sites on the skin and rapidly brings plasma concentrations to steady state. A crossover study comparing urinary excretion rates of scopolamine in healthy subjects over multiple 12-hour collection intervals showed no difference in drug excretion rates between constant-rate intravenous infusion (3.7–6 μg/h) and transdermal administration at steady state (24–72 hours). Transdermal delivery systems appear to deliver the drug into systemic circulation at the same rate as constant-rate intravenous infusion; however, the relatively long collection intervals (12 hours) make precise interpretation of the data difficult. Scopolamine excretion rates via transdermal systems were higher than those via constant-rate intravenous infusion within 12–24 hours and 72 hours post-administration. The distribution of scopolamine is not fully understood. The drug appears to bind reversibly to plasma proteins. Given its central nervous system effects, scopolamine is apparently capable of crossing the blood-brain barrier. The drug has been reported to cross the placenta and distribute into breast milk. Although the metabolic and excretory pathways of scopolamine are not fully understood, it is believed that the drug is almost entirely metabolized in the liver (primarily through conjugation) and excreted in the urine. In one study, only a small amount (approximately 4-5%) of a single oral dose of scopolamine was excreted unchanged in the urine within 50 hours; the urinary clearance of the unchanged drug was approximately 120 ml/min. In another study, 3.4% and less than 1% of a single dose, administered subcutaneously or orally, were excreted unchanged in the urine within 72 hours, respectively. In healthy individuals, after a single application of transdermal scopolamine (releasing approximately 1 mg within 72 hours), the urinary excretion rates of free scopolamine and total scopolamine (free and conjugated forms) were approximately 0.7 μg/h and 3.8 μg/h, respectively. Following removal of the transdermal patch, the consumption of scopolamine bound to skin receptors at the patch site led to a logarithmic linear decrease in plasma scopolamine concentration. Within 108 hours, less than 10% of the total dose was excreted in the urine as unchanged drug and its metabolites.

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Metabolism/Metabolites
Although multiple metabolites have been detected in animal studies, little is known about the metabolism of scopolamine in humans. Generally, scopolamine is primarily metabolized in the liver, with the main metabolites being various glucuronides and sulfide conjugates. Although the enzymes responsible for scopolamine metabolism are not fully understood, in vitro studies have shown that oxidative demethylation is associated with CYP3A subfamily activity, and the pharmacokinetics of scopolamine are significantly altered when co-administered with grapefruit juice, suggesting that CYP3A4 is at least partially involved in oxidative demethylation.
Although the metabolic and excretion pathways of scopolamine are not fully understood, the drug is believed to be almost entirely metabolized in the liver (primarily through conjugation) and excreted in the urine.
Elimination pathway: Less than 10% of the total dose is excreted in the urine as unchanged drug and its metabolites within 108 hours.
Half-life: 4.5 hours

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Biological half-life
The half-life of scopolamine varies depending on the route of administration. The half-lives for intravenous, oral, and intramuscular injections are 68.7 ± 1.0 minutes, 63.7 ± 1.3 minutes, and 69.1 ± 8.0 minutes, respectively, which are similar. The half-life for subcutaneous injection is longer, at 213 minutes. After removal of the transdermal patch, plasma concentrations of scopolamine decrease logarithmically, with a half-life of 9.5 hours.
After a single administration of the transdermal scopolamine system (releasing approximately 1 mg every 72 hours), the mean elimination half-life of the drug is 9.5 hours.

Toxicity Summary
Scopolamine works by interfering with the transmission of acetylcholine nerve impulses in the parasympathetic nervous system, particularly the vomiting center. Pregnancy and Lactation Effects ◉ Overview of Use During Lactation There is currently no information regarding the use of scopolamine during lactation. Use during labor appears to have an adverse effect on the newborn's breastfeeding behavior. Long-term use of scopolamine may reduce milk production or the milk ejection reflex, but a single systemic or ocular administration is unlikely to interfere with breastfeeding. During long-term use, signs of reduced milk production (e.g., dissatisfaction, poor weight gain) should be observed. To significantly reduce the amount of medication entering breast milk after using eye drops, press the tear duct at the corner of the eye for at least 1 minute, then wipe away any excess medication with absorbent tissue. ◉ Effects on Breastfed Infants As of the revision date, no relevant published information was found.
◉ Effects on Lactation and Breast Milk
Anticholinergic drugs can inhibit lactation in animals, possibly by suppressing the secretion of growth hormone and oxytocin. Anticholinergic drugs can also lower serum prolactin levels in non-lactating women. Prolactin levels in established lactating mothers may not affect their breastfeeding ability.
A retrospective case-control study conducted in two hospitals in central Iran compared breastfeeding behavior in the first two hours postpartum in four groups of infants born to healthy, full-term, singleton vaginal deliveries. Groups included: no medication received during delivery, oxytocin combined with scopolamine, oxytocin combined with meperidine, and oxytocin, scopolamine, and meperidine. Infants in the no-medication group performed better than all other groups, while the oxytocin combined with scopolamine group performed better than the meperidine group. Protein Binding Scopolamine reversibly binds to human plasma proteins. In rats, the plasma protein binding rate of scopolamine is relatively low, at 30 ± 10%. Interactions
Scopolamine should be used with caution in patients taking other medications that may cause central nervous system effects (e.g., sedatives, tranquilizers, or alcohol). Particular attention should be paid to potential interactions with drugs that have anticholinergic properties; for example, other belladonna alkaloids, antihistamines (including meclomethasone), tricyclic antidepressants, and muscle relaxants. Concomitant use of scopolamine may reduce the absorption of oral medications due to decreased gastric motility and delayed gastric emptying. Concomitant use of anticholinergic drugs and corticosteroids may lead to increased intraocular pressure. /Anticholinergic Drugs/Antispasmodics/ Concomitant use of antacids may reduce the absorption of some oral anticholinergic drugs. Therefore, oral anticholinergic drugs should be taken at least 1 hour before taking antacids. Taking anticholinergic drugs before meals can prolong the effect of postprandial antacids. However, controlled studies have failed to confirm a significant difference in gastric pH between the combined use of anticholinergic drugs and antacids and the use of antacids alone. /Antimuscarinic Drugs/Antispasmodics/
For more complete data on interactions of scopolamine (8 in total), please visit the HSDB records page.

[1]. Structure-activity requirements for hypotension and alpha-adrenergic receptor blockade by analogues of atropine. Eur J Pharmacol. 1983 May 20;90(1):75-83.

Therapeutic Uses
Adjunctive medication, anesthesia; antiemetic; muscarinic receptor antagonist; mydriatic; parasympathetic nerve blocker.
While transdermal scopolamine has been shown to reduce basal gastric acid secretion in healthy individuals and inhibit gastric acid secretion stimulated by betazazole, pentagastrin, and peptone, its effectiveness as an adjunct treatment for peptic ulcers has not been established. /This use is not currently included in the FDA-approved label./
Transdermal scopolamine has minimal antiemetic effect on chemotherapy-induced vomiting. /This use is not currently included in the FDA-approved label./
Scolophonium hydrobromide can be used as a mydriatic and cycloplegic agent, especially suitable for patients sensitive to atropine or in cases requiring shorter-term cycloplegia. Compared to atropine, this drug has a faster onset of action and a shorter duration of action. Scopolamine hydrobromide is also used to treat acute inflammation of the iris and uvea (e.g., iridocyclitis). /Scopolamine hydrobromide/
For more complete data on the therapeutic uses of scopolamine (10 in total), please visit the HSDB record page.

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Drug Warnings
The use of scopolamine to produce sedation and amnesia in various situations, including childbirth, is becoming less common, and its value is questionable. Use of scopolamine alone in cases of pain or severe anxiety may induce uncontrollable behavioral outbursts.
Therapeutic doses of scopolamine typically cause central nervous system depression, manifested as drowsiness, amnesia, fatigue, and dreamless sleep, and reduced rapid eye movement (REM) sleep.It also causes euphoria and is therefore prone to abuse. In the past, scopolamine was often used as an adjunct to anesthetics or as a pre-anesthetic medication, its sedative and amnesic effects being sought after. However, in cases of severe pain, the same dose of scopolamine can sometimes cause excitement, agitation, hallucinations, or delirium. These excitatory effects are similar to toxic doses of atropine. Following intramuscular or oral administration of scopolamine, salivary inhibition occurs within 30 minutes or 30 minutes to 1 hour, peaking within 1 hour or 1-2 hours; salivary inhibition can last for 4-6 hours. One study showed that after intravenous administration of a 0.6 mg dose, amnesia occurred within 10 minutes, peaked between 50 and 80 minutes, and lasted for at least 120 minutes after administration. In one study, intramuscular administration of 0.2 mg scopolamine produced an antiemetic effect within 15-30 minutes and lasted for approximately 4 hours. In another study, intramuscular administration of 0.1 or 0.2 mg scopolamine resulted in mydriasis that could last up to 8 hours. Transdermal delivery systems are designed to provide an antiemetic effect with an onset time of approximately 4 hours and a duration of action up to 72 hours. Low doses of scopolamine can inhibit sweat gland activity innervated by sympathetic cholinergic fibers, leading to hot and dry skin. Sweating may be suppressed, resulting in an increase in body temperature, but this is only noticeable with high doses or in warmer environments. For more complete data on scopolamine (21 in total), please visit the HSDB records page.
Pharmacodynamics
Scopolamine is an anticholinergic belladonna alkaloid that affects parasympathetic nervous system function by competitively inhibiting muscarinic receptors and acting on smooth muscle that is responsive to acetylcholine but lacks cholinergic innervation. Scopolamine is administered as a patch and provides sustained release over three days, becoming detectable in urine within 108 hours. Scopolamine is contraindicated in patients with angle-closure glaucoma. Because scopolamine can increase intraocular pressure, it should be used with caution in patients with open-angle glaucoma. In addition, scopolamine can cause a variety of neuropsychiatric side effects, including worsening of psychotic symptoms, seizures, seizure-like symptoms, and other psychiatric reactions and cognitive impairments. Scopolamine may impair a patient's ability to operate machinery or drive motor vehicles, engage in underwater sports, or perform any other potentially dangerous activities. Women with severe preeclampsia should avoid using scopolamine. Patients with gastrointestinal or urinary tract disorders should be closely monitored for functional impairments, and scopolamine should be discontinued immediately if related symptoms occur. Direct application of scopolamine to the eyes can cause blurred vision; therefore, transdermal patches should be removed before MRI scans to avoid skin burns. Due to its gastrointestinal effects, scopolamine may interfere with gastric secretion tests; therefore, it should be discontinued at least 10 days before the test. Finally, scopolamine may cause dependence and lead to nausea, dizziness, vomiting, gastrointestinal disturbances, sweating, headache, bradycardia, hypotension, and various neuropsychiatric symptoms after discontinuation; severe symptoms may require medical attention.

C17H21NO4

303.35

303.147

138-12-5

5184

Viscous liquid

0.827 g/mL at 25 °C(lit.)

196 °C(lit.)

−15 °C(lit.)

178 °F

0mmHg at 25°C

n20/D 1.429(lit.)

0.856

1

5

5

22

418

0

OCC(C1C=CC=CC=1)C(OC1CC2N(C)C(C3C2O3)C1)=O

STECJAGHUSJQJN-UHFFFAOYSA-N

InChI=1S/C17H21NO4/c1-18-13-7-11(8-14(18)16-15(13)22-16)21-17(20)12(9-19)10-5-3-2-4-6-10/h2-6,11-16,19H,7-9H2,1H3

(9-methyl-3-oxa-9-azatricyclo[3.3.1.02,4]nonan-7-yl) 3-hydroxy-2-phenylpropanoate

(-)-Scopolamine; scopalamine; scopolamine; 138-12-5; Atroscine; [(1S,2S,4R,5R)-9-methyl-3-oxa-9-azatricyclo[3.3.1.02,4]nonan-7-yl] 3-hydroxy-2-phenylpropanoate; 51-34-3; Benzeneacetic acid, alpha-(hydroxymethyl)-, 9-methyl-3-oxa-9-azatricyclo(3.3.1.0(2,4))non-7-yl ester, (1alpha,2beta,4beta,5alpha,7beta)-(+-)-;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)