What Is Carbachol?

Carbachol is carbachol chemical name 2-carbamyloxy-N, N, N-trimethylethylammonium chloride, white crystal; hygroscopic. It is very soluble in water, slightly soluble in ethanol, and almost insoluble in chloroform or ether. The melting point is 200-204 ° C, and it will decompose at the same time when melting. It should be ventilated and dried at low temperature and stored separately from food ingredients. It is a synthetic choline-like drug that can directly act on the pupil sphincter to produce an immediate pupil shrinking effect, and at the same time has an anti-cholinesterase effect, and can maintain a longer pupil shrinking time. It can also prevent the increase of intraocular pressure after ophthalmic surgery such as intraocular lens implantation and cataract extraction.

Carbachol is carbachol chemical name 2-carbamyloxy-N, N, N-trimethylethylammonium chloride, white crystal; hygroscopic. It is very soluble in water, slightly soluble in ethanol, and almost insoluble in chloroform or ether. The melting point is 200-204 ° C, and it will decompose at the same time when melting. It should be ventilated and dried at low temperature and stored separately from food ingredients. It is a synthetic choline-like drug that can directly act on the pupil sphincter to produce an immediate pupil shrinking effect, and at the same time has an anti-cholinesterase effect, and can maintain a longer pupil shrinking time. It can also prevent the increase of intraocular pressure after ophthalmic surgery such as intraocular lens implantation and cataract extraction.
Chinese name
Carbachol
Foreign name
Carbachol
State
Colorless clear liquid
Molecular formula
C6H15ClN2O2
Molecular weight
182.64800

Carbachol compounds

Carbachol Information

Chinese name: Carbachol
Chinese alias: Carbo
English name: carbachol
English alias: 2-carbamoyloxyethyl (trimethyl) azanium, chloride; (2-Hydroxyethyl) trimethylammonium chloride carbamate Carbachol Carbamylcholine chloride; Carbamoylcholine chloride; Carbachol, Carbamylcholine chloride; Carbamylcholine Chloride;
CAS number: 51-83-2
Molecular formula: C6H15ClN2O2
Molecular weight: 182.64800
Structural formula:
Exact mass: 182.08200
PSA: 52.32000 [1]

Carbachol physicochemical properties

Melting point: 210 ° C
Water solubility: 1.0 G / ML
Storage conditions: storerooms should be kept in a cool, dry, ventilated place and stored separately from food ingredients [1]

Carbachol production method

-chloroethanol is used as a raw material, and phosgene is acylated to obtain chloroformic acid--chloroethyl: it is then reacted with ammonia to form carbamate--chloroethyl, and finally reacted with trimethylamine to form a quaternary ammonium salt Carbachol: Another method of carbachol is to use choline chloride and urea as raw materials: when using the ratio of choline chloride: urea: sodium nitrite: sulfuric acid: 1: 1.15: 1.35, at 60 After about 40 hours of reaction, carbachol can be obtained in a yield of 71%. [1]

Carbachol use

This product is a choline-like drug and is also used as a parasympathetic stimulant. When used as a veterinary drug, it is used in large animals to treat acute abdominal pain in horses. [1]

Carbachol Safety Terminology

S26In case of contact with eyes, rinse immediately with plenty of water and seek medical advice.
After accidental contact with eyes, rinse immediately with plenty of water and seek medical advice.
S36 / 37 / 39Wear suitable protective clothing, gloves and eye / face protection.
Wear appropriate protective clothing, gloves and goggles or masks.
S45In case of accident or if you feel unwell, seek medical advice immediately (show the label whenever possible.)
In case of accident or if you feel unwell, seek medical advice immediately (show the label if possible).

Carbachol risk terminology

R25Toxic if swallowed.
Toxic if swallowed.
R36 / 37 / 38Irritating to eyes, respiratory system and skin.
Irritation of eyes, respiratory system and skin.

Carbachol Pharmacopoeia Standard

Carbachol main active ingredients

2-carbamyloxy-N, N, N-trimethylethylammonium. Calculated on dry basis, containing C6H15ClN2O2 shall not be less than 99.0%. [2]

Carbachol-like

White crystal; hygroscopic. It is very soluble in water, slightly soluble in ethanol, and almost insoluble in chloroform or ether. The melting point is 200-204 ° C, and it will decompose at the same time when melting. [2]

Carbachol identification

(1) Take about 50mg of this product, add 10ml of potassium hydroxide test solution made of ethanol, slowly heat and boil for 1 to 2 minutes, a white precipitate is formed, and ammonia smell can be smelled. The supernatant was decanted, and a few drops of 3 mol / L hydrochloric acid solution were added to the precipitate, and bubbles were generated.
(2) The infrared absorption spectrum of this product should be consistent with the reference spectrum.
(3) Identification of chlorides in aqueous solution of this product. [2]

Carbachol test

Loss on drying: Take this product and dry to constant weight at 105 . Lose weight should not exceed 2.0%. Ignition residue shall not exceed 0.1% [2]

Carbachol determination

Take about 0.15g of this product, accurately weigh, add 10ml glacial acetic acid and 40ml acetic anhydride to dissolve, titrate with perchloric acid titration solution (0.1mol / L) according to the potentiometric titration method, and correct the result of the titration with a blank test . Each 1ml of perchloric acid titration solution (0.1mol / L) is equivalent to 18.27mg of C6H15ClN2O2. [2]

Carbachol Pharmacology and Toxicology

This product is a synthetic choline-like drug, which can directly act on the pupil sphincter to produce an immediate pupil shrinking effect, at the same time, it has an anticholinesterase effect and can maintain a longer pupil shrinking time; it can also prevent artificial lens implantation, Increased intraocular pressure after cataract extraction and other ophthalmic surgery. The acute toxicity test results in mice showed that carbachol LD50 was 0.3 mg / kg by intravenous injection and 15 mg / kg by oral LD50. Ophthalmic topical application does not show systemic toxicity. The results of rabbit eye local toxicity test show that the product has no obvious damage to corneal endothelial cells, iris and ciliary body. [3]

Carbachol pharmacokinetics

This medicine is not easily inactivated by cholinesterase, so the duration of action is long. After eye drops, the pupil shrinkage effect occurs within 10-20 minutes, and it can last for 4-8 hours, and the intraocular pressure decreases for 8 hours. Intraocular injection in the anterior chamber has the largest miotic contraction effect within 2 to 5 minutes and can be maintained for 24 to 48 hours. [4]

Carbachol Indication

Carbachol is a synthetic choline-like drug with mild anticholinesterase action. Intraocular permeability is poor. The pupil narrows rapidly after the eye is clicked, and the effect is similar to that of pilocarpine, but the duration is about 3 times longer. It is suitable for ophthalmic surgery, such as intraocular lens implantation, cataract extraction, corneal transplantation, etc. Eye drops can be used to treat patients with open-angle glaucoma or allergic to pilocarpine alone, ineffective or tolerant. Non-ophthalmic preparations can be used for abdominal gas, urinary retention, and other abnormalities in the gastrointestinal or bladder after surgery, and can also be used to relieve dry mouth symptoms. [3]

Carbachol usage and dosage

Anterior chamber injection, 0.2 ~ 0.5ml once, as directed by your doctor
adult
· Conventional dose
· Intraocular administration
1. Preoperative medication: Inject the drug injection into the anterior chamber, once 0.02mg.
2. Glaucoma: 0.75% -1.5% eye drops, 2-3 times a day.
· Oral administration 2mg once a day, 3 times a day.
· Subcutaneous injection of 0.25 mg once, repeated once every 30 minutes if necessary, a total of 2 times.
[Foreign usage and dosage reference]
adult
· Conventional dose
· Intraocular administration
1. Glaucoma: (1) Primary open-angle glaucoma and other chronic glaucoma: The recommended initial dose is 0.75% -3% of eye drops, 2 drops at a time, 3 times a day, while adjusting the frequency and concentration of use In order to maintain intraocular pressure, prevent further damage to the optic nerve and further loss of visual field. (2) Nasolacrimal duct obstruction: Use 1.5% solution once every 12 hours.
2. Reduction of pupils in ophthalmic surgery: It is recommended to inject 0.01% of this medicine injection in the anterior chamber, and the maximum is not more than 0.5ml. [3]

Carbachol preparations and specifications

Carbachol tablets 2mg.
Carbachol injection (1) 1ml: 0.1mg. (2) 1ml: 0.25mg.
Storage method: sealed storage.
Carbachol eye drops 0.75% -3%.
[Storage] Keep it tightly closed.
Adverse reactions

Carbachol adverse reactions

After application of this product, there may be strong regulation of spasm, headache, conjunctival congestion, and increased lacrimal gland secretion. It also manifests as itching and twitching of the eyelids, and can increase blood flow to the iris and ciliary body. The above reactions can be more severe than when pilocarpine is used. There are also reports of cataracts.
Systemic reactions, adverse reactions of the cardiovascular system and blood are rare. Flushing, sweating, discomfort in the upper abdomen, cramps in the abdomen, snoring, tightness in the bladder, difficulty adjusting eyesight, headaches, and drooling can occur.
Common side effects are blurred vision, eye pain, eye irritation or burning; occasional side effects are headache, eye irritation or congestion, and eyelid twitching. The above symptoms usually disappear on their own. If persistent or serious adverse reactions occur, please seek medical treatment in time.
The cardiovascular system rarely causes systemic choline-like adverse reactions, but you should be alert for possible syncope, arrhythmia, or hypotension.
Headaches have been reported in the central nervous system and are more severe than pilocarpine use.
Vomiting and diarrhea were seen in the gastrointestinal tract.
Corneal turbidity, bullous keratitis and cataract have been reported in the eyes after corneal edema and iritis.

Carbachol drug interactions

This drug is used in combination with wetting drugs to enhance penetration. There were three reports of rapid cataract formation. Carbocholine is not effective when topical anti-inflammatory drugs are used concurrently in the eyes.

Carbachol overdose

Diarrhea, stomach cramps or pain, vomiting; syncope; flushing; frequent urination; sweating; arrhythmia; shortness of breath; asthma or chest tightness; abnormal fatigue or weakness; salivation.

Carbachol precautions

1. This medicine injection is contraindicated for intravenous or intramuscular injection.
2. Excessive medication can cause skin flushing, sweating, nausea, vomiting, salivation, abdominal discomfort, asthma attacks, substernal compression or pain, and severe cases can occur myocardial hypoxia, transient syncope and cardiac arrest, conduction block, Dyspnea, hypotension, involuntary bowel movements, and urgency.
3. Treatment of overdose: 0.5-1mg of atropine sulfate subcutaneously or intravenously. If severe cardiovascular or bronchoconstrictive reactions occur, subcutaneous or intramuscular injection of adrenaline 0.3-1mg can also be used. [3]

Carbachol contraindications

This product is contraindicated in patients with cardiovascular disorders including arrhythmia, bradycardia, hypotension, and patients with vagus nerve excitation, epilepsy, hyperthyroidism, Parkinson's disease, bronchial asthma, peptic ulcers, and urinary infarction.
1. Contraindications (1) Allergic to this medicine (foreign data). (2) Poor pupil shrinkage, such as acute irisitis (foreign data). (3) Hyperthyroidism. (4) Hypotension. (5) Peptic ulcer. (6) Bronchial asthma. (7) Arrhythmia and other heart diseases. (8) Epilepsy. (9) tremor paralysis. (10) Closed angle glaucoma. (11) Mechanical intestinal obstruction. (12) Urinary tract obstruction, spasms, etc. 2. Use with caution (1) Those with a history of retinal detachment (foreign data). (2) People who have corneal abrasions (this medicine may be absorbed in large quantities) (foreign data). (3) Those who have recently suffered a myocardial infarction (foreign data). (4) Patients with essential hypertension (foreign data). (5) Gastrointestinal spasm (foreign data).
3. The effects of the drug on pregnancy It is unclear whether this drug is harmful to the fetus. Pros and cons should be weighed during use during pregnancy. The U.S. Drug and Food Administration (FDA) rates the drug's pregnancy safety level C.
4. The effect of the drug on lactation It is unclear whether the drug is secreted into the milk and used with caution by lactating women.

Carbachol expert review

Carbachol is a synthetic choline-like drug with muscarinic and nicotinic effects similar to acetylcholine, and has a mild anticholinesterase effect, so the effect is longer lasting. After local eye drops, the ciliary muscles can contract, resulting in diminished pupils and accommodation spasms. The pupil shrinking effect is also obvious. It appears 10 to 20 minutes after the administration, and it can also reduce intraocular pressure. The effect of reducing intraocular pressure lasts for 8 hours. It is mostly used for clinical glaucoma. [4]

Carbachol Experimental Study

1. To study the effect of carbachol on intestinal vascular permeability and tissue edema during intestinal fluid replacement in scalded shock rats. Methods Forty-eight healthy male Wistar rats were randomly divided into a scalded group (S group), a glucose? Electrolyte group (GES group), a carbachol treatment group (CAR group), and a glucose-electrolyte + carbachol treatment group (GES / CAR group), 12 in each group. A 35% TBSA III ° burn model was made, and GES and / or CAR (60 g / kg) were input in the intestine for resuscitation. The modified Evans Blue (EB) exudation method was used to determine the intestinal vascular permeability during intestinal fluid replacement 4 hours after scald, and the change in intestinal tissue water content was measured by dry and wet weight method. Results Compared with the S group, the EB content of the intestinal tissue increased significantly (P <0.05), and the water content of the intestinal tissue increased, but there was no statistical significance (P> 0.05). After treatment with carbachol, the EB content in the intestinal tissue of the CAR group and the GES / CAR group was significantly lower than those of the S and GES groups, respectively (P <0.05). The intestinal tissue moisture content of the CAR group was lower than that of the S group (P <0.01), and the intestinal tissue water content of the GES / CAR group was significantly lower than that of the GES group (P <0.01). Conclusion Carbachol can reduce the intestinal vascular permeability during oral rehydration in scald shock, reduce intestinal mucosal tissue edema, and protect the small intestine ischemia-reperfusion injury during intestinal rehydration in scald shock.
2. To study the effect of carbachol (CAR), a pseudocholine drug, on gastric emptying and gastric blood flow during early oral glucose-electrolyte solution (GES) in rats with 40% blood volume loss. Methods Forty-eight male SD rats were randomly divided into: GES group (oral GES after surgery, n = 16), blood loss GES group (H GES, n = 16), and blood loss GES carbachol group (H GES / CAR, n = 16). After intramuscular anesthesia with ketamine-Sumianxin, the right carotid artery was intubated, and blood was released at intervals of 15 minutes at 40% of the systemic blood volume to make a hemorrhagic shock model. GES was administered twice at 0.5 hours and 1 hour after blood loss at twice the blood loss. Carbachol (60 g / kg)) was dissolved in GES and given at the first gastric administration. Laser Doppler flowmeter was used to measure the gastric tissue blood flow at 2 hours and 4 hours after blood loss, and gastric emptying rate was measured by phenol red method. Results At 2 hours and 4 hours after blood loss, the gastric emptying rate in the H GES group was 51.4% and 30.2% lower than that in the GES group (P <0.01 and P <0.05); the gastric blood flow was 50.0% and 35.2% lower (P <0.01) . The gastric emptying rate and gastric blood flow in the H GES / CAR group were significantly higher than those in the H GES group, and had returned to the GES group level 4 hours after injury (P> 0.05). Conclusion Carbachol can significantly increase the gastric emptying rate and gastric blood flow in early hemorrhagic shock in rats, and improve the effect of oral fluid resuscitation.
3. To explore the effects of different doses of carbachol on gastric blood flow and gastric emptying function in scalded rats. Methods: Forty male Wistar rats were randomly divided into a false iron group (n = 5) and a single iron group (n = 5) and oral carbachol group (n = 30), the latter is divided into 20, 40, 60, 80, 100, 120 g / kg group (5 per group) according to different carbachol doses. Rats were given intragastric administration of 1.5 ml of 0.1% phenol red solution. Rats in the single scald group and the oral carbachol group were given oral administration of 0.1 ml of phenol red solution after oral 30% TBSA degree burns, and the carbachol group was administered orally. The corresponding dose of carbachol + 1 ml of saline was administered to the stomach 0.5 h after injury. The rats were sacrificed 2 h after injury, and the effects of different doses of carbachol on gastric blood flow and gastric emptying rate in rats were observed. Results : The rate of gastric emptying in rats after burns was (29.50 ± 13.42)%, which was significantly lower than that in the sham burn group (92.19 ± 5.24)%, P <0.01. Gastric blood flow 2 hours after the injury was from that before the injury (476.00 ± 71.24) U decreased to (103.60 ± 51.28) U, P <0.01. Different doses of carbachol after scald can increase gastric emptying rate and gastric blood flow, but 60 g / kg is the most significant (P <0.01). Conclusion: card Bacholine can significantly promote gastric blood flow and gastric emptying in burn shock rats, and the optimal dose is 60 g / kg.
4. To explore the effect of carbachol on the plasma proinflammatory cytokine tumor necrosis factor alpha, interleukin 6 and anti-inflammatory cytokine interleukin 10 in rabbits with partial intestinal ischemia-reperfusion injury. Method: Experiment Completed at the 304 Hospital of the PLA in January 2005. 45 large-eared white rabbits were randomly divided into 20 carbachol treatment groups, 20 intestinal ischemia-reperfusion groups, and 5 sham-operated control groups. In the carbachol treatment group, carbachol was injected 30 mg / kg in the intestine 2 hours after partially blocking the superior mesenteric artery. The intestinal partial ischemia-reperfusion group blocked the superior mesenteric artery blood flow by 50% with a self-made blood blocker. Perfusion was restored after 4 hours. The sham operation control group did not block the superior mesenteric artery. Plasma proinflammatory cytokine tumor necrosis factor was measured before and after blocking 2, 4, 8 h, 1, 2, and 3 d, respectively. Contents of , interleukin 6 and anti-inflammatory cytokine interleukin 10. Results: 40 rabbits were entered into the result analysis experiment, 18 in the carbachol treatment group, 17 intestinal ischemia-reperfusion group, and sham operation control 5 rabbits. After partial intestinal ischemia-reperfusion injury in rabbits, plasma tumor necrosis factor and leukocytes The levels of interleukin 6 and interleukin 10 were significantly increased. After enteral injection of carbachol, the plasma tumor necrosis factor content decreased significantly at 1 d after operation, and the interleukin 6 content decreased significantly at 4 and 8 h after blocking. Compared with the intestinal partial ischemia-reperfusion group, the difference is significant. The intestinal ischemia-reperfusion group has no significant difference in plasma interleukin 10 content with the carbachol treatment group. The production and release of tumor necrosis factor alpha and interleukin 6, while the anti-inflammatory cytokine interleukin 10 has little effect. It shows that the pseudocholine drug-carbachol has a significant anti-inflammatory effect.
5. To study the anti-inflammatory and organ-protective effects of carbachol (cholinergic agonist) on sepsis models. Methods 128 rats were prepared by cecal ligation and puncture to prepare sepsis models. Randomly divided The carbachol group and the sepsis group were intravenously injected with 10 g · kg ~ (-1) or equivalent saline of carbachol, respectively. Observe the mortality rate, liver, kidney, heart function indexes, and pro-inflammatory factors at 12, 24 h. Level and tissue water content. Results The mortality rates at 12, 24 h in the carbachol group were 25% and 50%, which were significantly lower than the 37.5% and 75% in the sepsis group. The content of nitric oxide, myeloperoxide activity, organ function indexes and tissue water content were significantly lower in the carbachol group than in the sepsis group. Conclusion Carbachol can improve organ function and reduce early death in sepsis rats Rate, its mechanism may be related to its inhibition of pro-inflammatory factor levels, reduction of organ tissue inflammation and edema.
6. Objectives: 6.1 To observe the effects of carbachol on lipopolysaccharide-stimulated release of inflammatory cytokines from rat peritoneal macrophages; 6.2 to study the inhibition of carbachol on lipopolysaccharide stimulated rat peritoneal macrophages to release proinflammatory cytokine receptor pathways To provide experimental evidence for the prevention and treatment of carbachol in sepsis and multiple organ dysfunction such as excessive inflammatory diseases. Methods: Lipopolysaccharide (LPS, 100ng / mL) was used to stimulate rat peritoneal macrophage model, and the study was performed by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence. The research was conducted in two parts: 1. Effects of carbachol on LPS-stimulated macrophages to release inflammatory cytokines and comparison with other cholinergic receptor agonists. Peritoneal macrophages from male Wistar rats were adjusted to a concentration of 10-6 cells / mL. Well cell culture plate. Add carbachol (K1 2mmol / L, K2 0.2mmol / L, K3 0.02mmol / L, K4 2mol / L, K5 0.2mol / L, K6 0.02mol / L 6 concentrations), N-like choline Somatic agonist nicotine or M-like cholinergic receptor agonist muscarine, treated at room temperature for 15min; then added LPS to each well, and incubated in a 37 ° C, 5% CO_2 cell incubator for 4h . The concentrations of pro-inflammatory cytokines TNF-, IL-6 and anti-inflammatory cytokine IL-10 in the cell culture supernatant were detected. The experiment was divided into 5 groups: blank control group C; LPS control group, L; carbachol group, K; nicotine group, N; muscarinic group, M. In group K, 6 different concentrations of carbachol (K1-K6) were used to observe the difference in effect and determine the concentration of cholinergic receptor agonists in subsequent experiments. 2. Carbachol inhibits the receptor pathway of LPS-stimulated macrophages to release pro-inflammatory cytokines. Take the above concentrations of macrophages in a 24-well cell culture plate and add M-like cholinergic receptor antagonist atropine or N-like cholinergic Receptor 7 subunit (7nAChR) -specific antagonist -silver snake venom (-Bgt), incubated at room temperature for 15min; subsequent experimental steps are the same as the first part. The concentrations of TNF- and IL-6 in the cell culture supernatant were detected. The experiment was divided into 6 groups: carbachol group, K; nicotine group, N; atropine + carbachol group, AK: atropine + nicotine group, AN; silver ring snake toxin + carbachol group , BK; Agcyclotoxin + nicotine group, BN. Cells of the above concentrations were taken by immunofluorescence experiments, and cell slides were made in 6-well culture plates. First treat with carbachol or nicotine (5mmol / L) for 15min, then add fluorescein isothiocyanate (FITc) -labeled -Bgt (30g / mL), and incubate at 4 ° C for 15min. After rinsing and sealing, observe the fluorescence intensity and take pictures under a fluorescence microscope and a laser scanning confocal microscope. The experiment was divided into 4 groups: negative control group; positive control group: cells labeled with FITC--Bgt alone; nicotine control group: nicotine + FITC--Bgt; carbachol group: carbachol + FITC--Bgt. Results: 1. Normal rat peritoneal macrophages expressed a small amount of various cytokines including TNF-, IL-6 and IL-10 in vitro in RPMI1640 medium; after LPS stimulation, the levels of these three cytokines increased significantly compared with the blank control group. 2. After treating macrophages with 6 concentrations of K1-K6 carbachol, the levels of TNF- in each concentration group were lower than those in L group. Among them, the K1, K2, and K3 groups were significantly different from the L group. K3 was selected as the cholinergic receptor agonist concentration in subsequent experiments. 3 Compared with the L group, the TNF- and IL-6 levels in the K group were significantly reduced, and the IL-10 levels were not significantly changed. 4 The levels of TNF- and IL-6 in the K, N, and M groups were significantly lower than those in the L group; compared with the M group, the K and N groups decreased more significantly; there was no significant difference between the K and N groups. Compared with the L group, there were no significant changes in IL-10 levels in the K and N groups. 5. Compared with the K group, the levels of TNF- and IL-6 in the AK group were not significantly changed; compared with the N group, the levels of TNF- and IL-6 were not significantly changed in the AN group; compared with the K group, the TNF- in the BK group Alpha and IL-6 levels were significantly increased; similarly, TNF- and IL-6 levels were significantly increased in the BN group compared to the N group. 6. Results of immunofluorescence experiments. After FITC--Bgt labeling, obvious fluorescence can be seen at the cell membrane position; however, after being treated with high concentration of nicotine and carbachol and then labeled with FITC--Bgt, the fluorescence intensity on the cell surface is significantly reduced. Conclusions: 1. Carbachol can significantly inhibit the release of TNF- and IL-6 by LPS-stimulated peritoneal macrophages in rats in a dose-dependent manner, but has no significant effect on the level of IL-10; 2. The inflammatory effect is similar to nicotine, both of which are significantly stronger than muscarin; 3, -Bgt can significantly reduce the binding of carbachol and nicotine to macrophage surface receptors, thereby inhibiting their anti-inflammatory effects, while atropine's The effect is not obvious, indicating that carbachol exerts anti-inflammatory effects through 7nAChR.

Carbachol toxicity

Toxicity data from literature and journals
Numbering
Toxicity type
testing method
Test object
Dosage used
Toxic effect
1
Acute toxicity
Intravenous injection
Adult male
1428 ng / kg
1. Vascular toxicity-decreased blood pressure regulation 2. Vascular toxicity-local or systemic arterial and venous dilation 3. Gastrointestinal toxicity-nausea, vomiting
2
Acute toxicity
Intramuscular injection
Humanity
6 ug / kg
1. Eye toxicity-tearing 2. Vascular toxicity-local or systemic arterial and venous dilation 3. Skin and accessory toxicity-sweating
3
Acute toxicity
Intramuscular injection
Adult male
2857 ng / kg
1. Vascular toxicity-decreased ability to regulate blood pressure
4
Acute toxicity
oral
Rat
40 mg / kg
Detailed effects are not reported other than lethal dose
5
Acute toxicity
Intraperitoneal injection
Rat
2 mg / kg
1. Cerebral toxicity-affects the central nervous system in specific areas 2. Autonomic toxicity-problems with sympathetic nerves 3. Behavioral toxicity-excitement
6
Acute toxicity
Subcutaneous injection
Rat
4 mg / kg
Detailed effects are not reported other than lethal dose
7
Acute toxicity
Intravenous injection
Rat
100 ug / kg
Detailed effects are not reported other than lethal dose
8
Acute toxicity
oral
Mouse
15 mg / kg
Detailed effects are not reported other than lethal dose
9
Acute toxicity
Intraperitoneal injection
Mouse
50 ug / kg
1. Behavioral toxicity-lethargy 2. Behavioral toxicity-convulsions or seizure thresholds affected 3. Lung, chest or respiratory toxicity-other changes
10
Acute toxicity
Subcutaneous injection
Mouse
3 mg / kg
Detailed effects are not reported other than lethal dose
11
Acute toxicity
Intravenous injection
Mouse
300 ug / kg
Detailed effects are not reported other than lethal dose
12
Acute toxicity
oral
dog
3 mg / kg
1. Gastrointestinal toxicity-changes in the structure or function of salivary glands 2. Gastrointestinal toxicity-nausea, vomiting
13
Acute toxicity
Subcutaneous injection
dog
100 ug / kg
1. Gastrointestinal toxicity-changes in the structure or function of salivary glands 2. Gastrointestinal toxicity-Excessive exercise, diarrhea 3. Gastrointestinal toxicity-Nausea, vomiting
14
Acute toxicity
Subcutaneous injection
Guinea Pig
75 ug / kg
1. Behavioral toxicity-changes in sleep time (including changes in righting reflex)
2. Toxicity of the nutritional and metabolic systems-decreased body temperature
15
Acute toxicity
Not reported
frog
5 mg / kg
1. Peripheral neurotoxicity-spastic paralysis or no change in sensation 2. Behavioral toxicity-changes in sleep time (including changes in righting reflex)
3. Cardiotoxicity-other changes
[5-10]

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