Nicotinic cholinoceptor
Anisodamine acts as a non‑subtype‑selective muscarinic acetylcholine receptor (mAChR) antagonist (including M1, M2, M3 subtypes) and also as a nicotinic acetylcholine receptor (nAChR) antagonist. [1]
In mouse brain homogenates, anisodamine competitively displaced ³H‑quinucidinyl benzilate (QNB) with an IC₅₀ of 72.0 ± 1.7 μM, whereas scopolamine showed an IC₅₀ of 0.18 ± 0.02 μM. [1]

Anisodamine pretreatment (100 μg/mL; 20 minutes; RAW264.7 cells) significantly attenuates the average fluorescence intensity of α-bungarotoxin binding compared to Ach alone[2].
Anisodamine may act by blocking muscarinic receptors, which in turn increases the amount of endogenous ACh that binds to the α-7nAChR[2].

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Anisodamine protected cultured bovine pulmonary endothelial cells from injury induced by oxygen free radicals, with no evidence of direct radical scavenging, suggesting a membrane‑stabilizing effect. [1]
In rat pulmonary microvascular endothelial cells (PMVECs) exposed to lipopolysaccharide (LPS), anisodamine reduced the expression of IL‑17A and IL‑17F. [1]
In isolated adult rat ventricular myocytes, anisodamine inhibited cardiomyocyte contractility and the transient rise in intracellular Ca²⁺ concentration, and also depressed contraction evoked by the muscarinic agonist carbachol. [1]
Anisodamine inhibited the uptake of Ca²⁺ by skeletal muscle sarcoplasmic reticulum Ca²⁺ ATPase, possibly by inducing structural modification of the transmembrane domain. [1]
In human endothelial cells, anisodamine counteracted LPS‑induced tissue factor and plasminogen activator inhibitor‑1 expression via the NF‑κB pathway. [1]
Anisodamine inhibited platelet aggregation in vitro, and also inhibited thromboxane synthesis. [1]

Anisodamine (50 mg/kg; intraperitoneally; 72 hours) significantly lowers mortality to 20%[2].

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In a mouse model of scopolamine‑induced cognitive impairment, anisodamine (20 mg·kg⁻¹) ameliorated the peripheral muscarinic side effects (salivation, enhanced bowel movement, bradycardia) of pilocarpine while preserving cognitive improvement. [1]
In mice injected with scopolamine and treated with rivastigmine, anisodamine counteracted rivastigmine‑induced hypersalivation, hyperperistalsis and muscle cramps, and facilitated cognitive amelioration. [1]
In a severe organophosphate‑poisoned patient, after high‑dose atropine failed, anisodamine (total 480 mg i.v. over 4 hours, then 20 mg four times on the next day) restored blood gases to normal and allowed extubation on day 5. [1]
In a retrospective analysis of 64 organophosphate‑poisoned patients who failed to achieve atropinization after 12 h of high‑dose atropine, switching to anisodamine (group of 28 patients) shortened time to atropinization (24.3±4.3 h vs. 29±7.0 h, P<0.05) and reduced hospital stay (5.3±2.5 days vs. 6.9±2.3 days, P<0.05) compared to continuing atropine. [1]
In a rat model of perfluoroisobutylene (PFIB)‑induced acute lung injury, high‑dose anisodamine (30 mg·kg⁻¹) attenuated pulmonary oedema (decreased wet lung/body weight ratio, dry lung/body weight ratio, and total protein concentration). [1]
In a swine model of cardiac arrest, anisodamine‑treated animals had significantly lower plasma malondialdehyde, higher superoxide dismutase and ATP, lower mitochondrial ROS, and milder mitochondrial injury compared to controls and an adrenaline‑treated group. [1]
In a mouse model of ovalbumin‑induced asthma, anisodamine suppressed peribronchial and perivascular eosinophil infiltration, attenuated airway epithelial hyperplasia and basement membrane thickening, and shifted the Th1/Th2 balance (down‑regulation of IL‑4, up‑regulation of IFNγ). [1]
In a rat model of LPS‑induced acute lung injury, anisodamine reduced lung injury and IL‑17A/IL‑17F expression comparably to methylprednisolone. [1]
In a canine cardiopulmonary bypass model, anisodamine reduced lung water content, pulmonary granulocyte sequestration and oxygen free‑radical release. [1]
In rabbits, anisodamine dilated both pulmonary and systemic vessels (relatively weak effect). [1]
In rabbits, anisodamine decreased adrenaline‑induced ventricular tachycardia. [1]
In a rat model of ischaemia‑reperfusion, anisodamine reduced cardiomyocyte apoptosis. [1]

Receptor binding assay: Mouse brain homogenates were incubated with varying concentrations of anisodamine or scopolamine together with ³H‑quinucidinyl benzilate (QNB). After incubation, bound radioactivity was measured by filtration or centrifugation. The concentration of anisodamine that displaced 50% of specifically bound ³H‑QNB (IC₅₀) was determined to be 72.0 ± 1.7 μM. [1]
Ca²⁺‑ATPase activity assay: The effect of anisodamine on Ca²⁺ uptake by skeletal muscle sarcoplasmic reticulum Ca²⁺ ATPase was studied. Anisodamine was found to inhibit Ca²⁺ uptake, possibly by altering the transmembrane domain structure of the enzyme. [1]

Bovine pulmonary arterial endothelial cells were cultured and exposed to oxygen free radicals. Anisodamine protected these cells from injury, and the protection was not due to direct radical scavenging but rather to membrane stabilization. [1]
Rat pulmonary microvascular endothelial cells (PMVECs) were treated with lipopolysaccharide (LPS) in the presence or absence of anisodamine. Anisodamine reduced the expression of IL‑17A and IL‑17F. [1]
Isolated adult rat ventricular myocytes were used to measure cell contraction and intracellular Ca²⁺ transients. Anisodamine inhibited basal contractility and the rise in Ca²⁺ induced by the muscarinic agonist carbachol. [1]
Human endothelial cells were stimulated with LPS. Anisodamine counteracted the LPS‑induced expression of tissue factor and plasminogen activator inhibitor‑1, and this effect involved the NF‑κB pathway. [1]

LPS-Induced Shock Mice
50 mg/kg
I.p.

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Mouse model of scopolamine‑induced cholinergic deficit: Mice were injected with scopolamine (dose not specified in the review) and then treated with pilocarpine (20 or 40 mg·kg⁻¹ i.p. twice daily) together with anisodamine (20 mg·kg⁻¹). Anisodamine ameliorated muscarinic side effects. [1]
Mouse model of rivastigmine adverse effects: Mice received scopolamine and rivastigmine (dose not specified) plus anisodamine (20 mg·kg⁻¹). Anisodamine counteracted hypersalivation, hyperperistalsis and muscle cramps. [1]
Retrospective clinical study in organophosphate‑poisoned patients: 28 patients who failed atropinization after 12 h of high‑dose atropine received anisodamine treatment (protocol details not fully specified in the review). [1]
Rat model of PFIB‑induced acute lung injury: Rats were exposed to perfluoroisobutylene (PFIB) and then treated with anisodamine at 30 mg·kg⁻¹ (route not specified). Pulmonary oedema parameters were assessed. [1]
Swine model of cardiac arrest: Swine were subjected to cardiac arrest and then treated with anisodamine (dose not specified). Plasma malondialdehyde, superoxide dismutase, ATP, and mitochondrial ROS were measured. [1]
Mouse model of ovalbumin‑induced asthma: Mice were sensitized and challenged with ovalbumin. Anisodamine (dose not specified) was administered, and airway inflammation, eosinophil infiltration, Th1/Th2 cytokine levels and airway remodelling were assessed. [1]
Rat model of LPS‑induced acute lung injury: Rats were treated with intratracheal LPS, and anisodamine (dose not specified) was given. Lung injury and IL‑17A/IL‑17F expression were evaluated. [1]
Canine cardiopulmonary bypass model: Dogs undergoing cardiopulmonary bypass received anisodamine infusion (dose not specified). Lung water content, granulocyte sequestration and free‑radical release were measured. [1]
Rabbit model of oleic acid‑induced lung injury: Rabbits exposed to oleic acid were treated with anisodamine (dose not specified), and lung protection was observed. [1]

The octanol‑water partition coefficient (logP) of anisodamine is 0.25, indicating low lipid solubility compared to scopolamine (logP 0.76). [1]
Anisodamine has limited blood‑brain barrier permeability due to its low lipid solubility, which results in lower central effects and less impairment of learning and memory compared with atropine and scopolamine. [1]

Anisodamine is less toxic than atropine and scopolamine based on animal studies. [1]
The usual human therapeutic dose is 10 mg·kg⁻¹, and doses as high as 500 mg·kg⁻¹·day⁻¹ did not produce any serious adverse effects. [1]
In a neuropsychopharmacological study in mice, anisodamine did not cause spatial cognitive deficits (assessed by Morris water maze) and did not depress long‑term potentiation (LTP) recordings in rats, whereas scopolamine had detrimental effects. At repeated high doses, anisodamine even improved cognition. [1]
In a human safety study (phase I) of rivastigmine, adverse effects prevented its use alone as a prophylactic against nerve agents; the combination with anisodamine is proposed to reduce those adverse effects. [1]

[1]. Possible role for anisodamine in organophosphate poisoning. Br J Pharmacol. 2016 Jun;173(11):1719-27.

[2]. Antishock effect of anisodamine involves a novel pathway for activating alpha7 nicotinic acetylcholine receptor. Crit Care Med. 2009;37(2):634-641.

Anisodamine has been investigated for its use in treating intestinal diseases. 6-HydroxyAnisodamine has been reported in Duboisia myoporoides, Hyoscyamus albus, and Anisodus tanguticus, with relevant data available. See also: 6-HydroxyAnisodamine (note moved to).

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Anisodamine has long been considered an antidote in organophosphate poisoning in China and Tibet. It is less potent than scopolamine at inducing central effects and, in septic shock, showed fewer adverse effects than atropine. [1]
Mechanisms of action beyond anticholinergic effects include anti‑inflammatory activity (e.g., reducing TNF‑α, IL‑1β, IL‑17A/IL‑17F, and up‑regulating α7nAChR via IL‑10), antioxidant activity (reducing oxidative stress and protecting mitochondria), membrane stabilization, anti‑arrhythmic effects, anti‑thrombotic/fibrinolytic effects (inhibiting platelet aggregation and thromboxane synthesis), and improvement of microcirculation (vasodilation via α1‑adrenoceptor blockade and other mechanisms). [1]
Anisodamine has been shown to be protective in animal models of septic shock, acute lung injury, asthma, arthritis, cardiac arrhythmias, ischaemia‑reperfusion injury, and toxic shock syndrome. [1]
The combination of anisodamine with neostigmine produced synergistic anti‑shock effects in LPS‑treated rats and haemorrhagic shock in beagle dogs, allowing lower doses of each drug and reducing neostigmine’s adverse effects. [1]

C17H23NO4

305.36882

305.163

C, 66.86; H, 7.59; N, 4.59; O, 20.96

55869-99-3

Anisodamine hydrobromide; 55449-49-5; Anisodamine hydrochloride; 131674-05-0

6918612

White to off-white solid powder

1.27

423.1ºC at 760 mmHg

1.565

0.839

2

5

5

22

396

5

CN1[C@H]2[C@@H](O)C[C@@H]1C[C@H](OC([C@@H](C3=CC=CC=C3)CO)=O)C2

WTQYWNWRJNXDEG-RBZJEDDUSA-N

InChI=1S/C17H23NO4/c1-18-12-7-13(9-15(18)16(20)8-12)22-17(21)14(10-19)11-5-3-2-4-6-11/h2-6,12-16,19-20H,7-10H2,1H3/t12-,13-,14+,15+,16-/m0/s1

[(1R,3S,5R,6S)-6-hydroxy-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] (2S)-3-hydroxy-2-phenylpropanoate

6-Hydroxy hyoscyamine; 654 II; 654-II; 654II

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)

DMSO: ≥ 100 mg/mL (~327.5 mM)
H2O: ~20 mg/mL (~65.5 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.19 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (8.19 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (8.19 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 50 mg/mL (163.74 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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