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TETRAHYDROPALMATINE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Tetrahydropalmatine is a tetrahydroprotoberbine alkaloid used in herb drugs (Jin, 1987). Other members of this class of agents are listed below. They differ in having different hydroxyl groups substituted for methoxy groups (Xuan et al, 1988).

Specific Substances

    A) TETRAHYDROPALMATINE
    1) Tetrahydropalmatine
    L-TETRAHYDROPALMATINE HYDROCHLORIDE
    1) Berberine, 2,3,9,10-tetramethoxy-, hydrochloride
    2) Caseanine
    3) Gindarine
    4) Molecular Formula: C21-H25-N-04.HCl
    5) Rotundine (levo form of tetrahydropalmatine)
    6) CAS 2506-20-9
    7) CAS 35067-82-4
    8) NIOSH/RTECS DR 9825000
    9) Wiswesser Notation: T D6 B666 KN&TT&J G01 H01 P01
    10) 01 & GH
    D-TETRAHYDROPALMATINE HYDROCHLORIDE
    1) Berberine, 2,3,9,10-tetramethoxy-, hydrochloride (+)
    2) Molecular Formula: C21-H25-N-04.HCl
    3) Palmatine, tetrahydro-, hydrochloride
    4) CAS 6024-83-5
    5) NIOSH/RTECS DR 9830000
    6) Wiswesser Notation: T D6 B666 KN&TT&J G01 H01 P01 Q01 & GH
    SPECIFIC TETRAHYDROBERBERINES
    1) (-) Corydalmine (l-CDL)
    2) (+/-) Corypalmine
    3) (-) Scoulerine
    4) (-) Stepholidine ((-) SPD, l-SPD)
    5) (+/-) Tetrohydroberberine (THB)
    6) (-) Tetrahydropalmatine ((-)THP)

Available Forms Sources

    A) SOURCES
    1) CORYDALIS AMBIGUA: The racemic form is found primarily in Corydalis ambigua root (deSmet et al, 1989), which is used as an analgesic in many traditional Chinese drugs (Jin, 1987).
    2) CORYDALIS PLATYCARPA: Is known to contain at least 7 kinds of alkaloids, including d-corybulbine, cheilanthifoline, l-capaurine, sanguinarine, and protopine (Tani et al, 1970).
    3) CORYDALIS TUBER (YUANHU OR YANHUSUO): Corydalis tuber from Corydalis turtschaninovii Bess f yanhusuo contains about 20 different alkaloids, including dl-tetrahydropalmatine (Yu & Keli, 1987).
    4) STEPHANIA ROTUNDA: Various analogues of tetrahydropalmatine have been isolated from Stephania species. The root tuber of Stephania rotunda was found to contain l-tetrahydropalmatine, stepharine, and stepharotine (86:460-466).
    5) HERBAL PRODUCTS: Jin Bu Huan Anodyne tablets were found in some cases to contain approximately 28.8 mg of THP, even though this product was labelled as having Polygala chinensis, which has no THP (deSmet et al, 1989; RMPDC, 1993; Horowitz et al, 1993).
    B) USES
    1) Jin Bu Huan tablets have been used in China for pain relief. Besides its analgesic effects it also has hypnotic properties (Horowitz et al, 1993; Lai & Chan, 1999). It has also been labelled by the manufacturer to be useful for the treatment of "insomnia due to pain, ulcer, stomachache, neuralgia, pain in shrunken womb after childbirth, nervous insomnia, and spasmodic cough" ((FDA, 1993)).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) There have been only a few overdose cases, characterized by CNS depression, lethargy, flaccidity, and coma. Bradycardia and apnea may develop. Onset is rapid, duration is less than 12 hours.
    1) Hepatitis has been reported with therapeutic doses of a Chinese herbal product, Jin Bu Huan.
    0.2.3) VITAL SIGNS
    A) Bradycardia, hypotension and respiratory depression have been reported after overdose in children; lethargy and disorientation have occurred in adults following overdose.
    0.2.5) CARDIOVASCULAR
    A) Blood pressure and heart rate may be decreased.
    0.2.6) RESPIRATORY
    A) Respiratory depression may lead to apnea.
    0.2.7) NEUROLOGIC
    A) CNS depression is seen. Therapeutic amounts have a tranquilizing or hypnotic effect; overdose may result in coma.
    0.2.9) HEPATIC
    A) Hepatitis has been associated with the Chinese herbal product, Jin Bu Huan.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.
    0.2.22) OTHER
    A) THP catalepsy is enhanced by scopolamine and diminished by physostigmine.

Laboratory Monitoring

    A) Few specific laboratory measures are indicated, as there are few case reports to evaluate.
    B) Hepatotoxicity has been associated with Jin Bu Huan chronic ingestion. Monitor serum liver function tests as indicated.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) No specific antidote is available. Treatment is symptomatic and supportive. Atropine may be used for bradycardia. Intubation and respiratory support may be necessary due to rapid onset of respiratory depression following ingestion. Generally, effects last approximately 8 to 12 hours.
    B) EMESIS/NOT RECOMMENDED: Because of rapid onset of CNS depression (30 minutes in animal experiments), emesis is NOT indicated. Decontamination may be attempted with activated charcoal.
    C) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    D) ATROPINE: ADULT DOSE: BRADYCARDIA: BOLUS: 0.5 mg IV may repeat every 3 to 5 min. Maximum: 3 mg. PEDIATRIC DOSE: 0.02 mg/kg IV/IO (0.04 to 0.06 mg/kg ET). Repeat once, if needed. Minimum dose: 0.1 mg. Maximum single dose: Child: 0.5 mg; Adolescent: 1 mg. Maximum total dose: Child: 1 mg; Adolescent: 2 mg.
    E) APNEA - Aggressive respiratory support, including intubation, may be required.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) OVERDOSE DATA
    1) PEDIATRIC - Three children ingested between 7 and 60 tablets of Jin Bu Huan containing 36% levo tetrahydropalmatine and developed CNS, cardiovascular, and respiratory depression. The children developed no permanent sequelae.
    2) ADULTS - Two adults ingested between 60 to 75 sleeping pills containing approximately 25 milligrams/tablet (approximate dose 1500 to 1875 milligrams) of tetrahydropalmatine, and developed initial central nervous system depression; long term sequelae was NOT reported.
    B) ANIMAL DATA
    1) CATS - An intravenous 40 milligram/kilogram dose slightly dropped blood pressure and heart rate, but did not affect cardiac function significantly.
    2) RABBITS - Doses of 20 to 40 milligrams/kilogram intravenously provided a transient respiratory stimulation, while 60 milligrams/kilogram intravenously depressed respiration.

Clinical Effects

Summary Of Exposure

    A) There have been only a few overdose cases, characterized by CNS depression, lethargy, flaccidity, and coma. Bradycardia and apnea may develop. Onset is rapid, duration is less than 12 hours.
    1) Hepatitis has been reported with therapeutic doses of a Chinese herbal product, Jin Bu Huan.

Vital Signs

    3.3.1) SUMMARY
    A) Bradycardia, hypotension and respiratory depression have been reported after overdose in children; lethargy and disorientation have occurred in adults following overdose.
    3.3.3) TEMPERATURE
    A) FEVER has been reported in adults who developed hepatitis after chronic use of Jin Bu Huan (Woolf et al, 1994).

Cardiovascular

    3.5.1) SUMMARY
    A) Blood pressure and heart rate may be decreased.
    3.5.2) CLINICAL EFFECTS
    A) BRADYCARDIA
    1) Acute episodes of bradycardia have been reported in pediatric overdose. Atropine was required for a sudden drop in heart rate into the 30's (RMPDC, 1993; Feldhaus et al, 1993).
    2) The bradycardia may be due to inhibition of potential-dependent calcium channel, and norepinephrine induced release of intracellular calcium storage (Zhao et al, 1988).
    3) THP has shown antidysrhythmic effects against ouabain, calcium chloride-ACh, picrotoxin, and electrically induced tachydysrhythmias (Wang & Li, 1987).

Respiratory

    3.6.1) SUMMARY
    A) Respiratory depression may lead to apnea.
    3.6.2) CLINICAL EFFECTS
    A) APNEA
    1) Apnea has been reported in children (RMPDC, 1993; Feldhaus et al, 1993).

Neurologic

    3.7.1) SUMMARY
    A) CNS depression is seen. Therapeutic amounts have a tranquilizing or hypnotic effect; overdose may result in coma.
    3.7.2) CLINICAL EFFECTS
    A) CATATONIC REACTION
    1) Catalepsy may be induced by high doses of THP
    2) Catalepsy may be due to depletion of dopamine from the limbic area and striatum (Wang & Liu, 1985).
    B) CENTRAL NERVOUS SYSTEM DEFICIT
    1) Hypnotic effects are seen in most animal species studied (Chang & But, 1986), and humans (deSmet et al, 1989).
    2) In a 13-month-old male overdose, CNS depression, flaccidity, lethargy, and coma were seen. Treatment included GI decontamination with activated charcoal; naloxone was given with NO response. Effects lasted less than 12 hours as the toddler became more alert (RMPDC, 1993).
    C) DROWSY
    1) CASE REPORT - Somnolence and disorientation were reported in a 28-year-old following an ingestion of 75 sleeping tablets (Rohypson) containing THP (approximately 25 mg/tablet) and zopiclone (a non-benzodiazepine hypnotic agent; amount not reported). Long-term effects were NOT reported (Lai & Chan, 1999).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) SOMNOLENCE
    a) DOGS - After a subcutaneous injection (dose not stated), dogs will fall asleep after 5 to 20 minutes. Duration is about 80 minutes (Bensky & Gamble, 1986).
    1) THP will prolong the sedative effect of barbiturates (Bensky & Gamble, 1986).
    2) OTHER NON-SPECIFIC
    a) MICE - Antagonizes the effects of mescaline (Bensky & Gamble, 1986).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA
    1) Nausea is described in patients who developed hepatitis associated with chronic use of the herbal product Jin Bu Huan (Woolf et al, 1994).

Hepatic

    3.9.1) SUMMARY
    A) Hepatitis has been associated with the Chinese herbal product, Jin Bu Huan.
    3.9.2) CLINICAL EFFECTS
    A) TOXIC HEPATITIS
    1) Hepatitis in an adult has been associated with the Chinese herbal product, Jin Bu Huan, ingested in doses recommended by the package insert for 25 days prior to symptoms (Horowitz et al, 1994).
    2) Seven other cases of hepatitis associated with the chronic use of Jin Bu Huan have been reported. Effects occurred after a mean of 20 weeks ingestion (range, 2 to 30 weeks) and resolved within a mean of 8 weeks (Woolf et al, 1994).
    3) Chronic hepatitis was confirmed in a 49-year-old male following several months of therapeutic use of Jin Bu Huan. Liver function tests normalized following drug cessation (Picciotto et al, 1998).

Endocrine

    3.16.2) CLINICAL EFFECTS
    A) DISORDER OF ENDOCRINE SYSTEM
    1) Tetrahydropalmatine is thought to stimulate the release of ACTH from the pituitary (Bensky & Gamble, 1986).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

Genotoxicity

    A) At the time of this review, no data were available to assess the mutagenic or genotoxic potential of this agent.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Few specific laboratory measures are indicated, as there are few case reports to evaluate.
    B) Hepatotoxicity has been associated with Jin Bu Huan chronic ingestion. Monitor serum liver function tests as indicated.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Overdose experience is limited. Monitor serum liver function tests as hepatotoxicity has been associated with the therapeutic use (toxicity has developed in as little as 4 weeks) of the Chinese herbal medicine, Jin Bu Huan.
    a) In limited case reports of hepatotoxicity, alterations in coagulation studies were not documented.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) Institute continuous cardiac monitoring and monitor for respiratory depression and hypoxia.

Methods

    A) SPECTROSCOPY/SPECTROMETRY
    1) Tetrahydropalmatine can be identified using nuclear magnetic resonance and mass spectrometry with infrared spectrum detection (deSmet et al, 1989).
    B) CHROMATOGRAPHY
    1) Lai & Chan (1999)reported the use of gas chromatography-mass spectrometry for the detection of tetrahydropalmatine in serum and urine in a small group of patients intoxicated by tetrahydropalmatine.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Few specific laboratory measures are indicated, as there are few case reports to evaluate.
    B) Hepatotoxicity has been associated with Jin Bu Huan chronic ingestion. Monitor serum liver function tests as indicated.

Oral Exposure

    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Because of rapid onset of CNS depression (30 minutes in animal experiments), emesis is NOT indicated, either at home or the emergency department. Decontamination may be attempted with activated charcoal.
    B) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) Treatment is primarily supportive; no specific antidote available. Respiratory support and intubation may be necessary following a significant exposure due to the rapid onset of respiratory depression. Atropine may be useful for bradycardia. Generally, effects are between 10 and 12 hours duration in most documented cases of overdose.
    B) BRADYCARDIA
    1) Atropine has been used successfully following overdose (RMPDC, 1993).
    2) ATROPINE/DOSE
    a) ADULT BRADYCARDIA: BOLUS: Give 0.5 milligram IV, repeat every 3 to 5 minutes, if bradycardia persists. Maximum: 3 milligrams (0.04 milligram/kilogram) intravenously is a fully vagolytic dose in most adults. Doses less than 0.5 milligram may cause paradoxical bradycardia in adults (Neumar et al, 2010).
    b) PEDIATRIC DOSE: As premedication for emergency intubation in specific situations (eg, giving succinylchoine to facilitate intubation), give 0.02 milligram/kilogram intravenously or intraosseously (0.04 to 0.06 mg/kg via endotracheal tube followed by several positive pressure breaths) repeat once, if needed (de Caen et al, 2015; Kleinman et al, 2010). MAXIMUM SINGLE DOSE: Children: 0.5 milligram; adolescent: 1 mg.
    1) There is no minimum dose (de Caen et al, 2015).
    2) MAXIMUM TOTAL DOSE: Children: 1 milligram; adolescents: 2 milligrams (Kleinman et al, 2010).
    C) AIRWAY MANAGEMENT
    1) Aggressive respiratory support, including possible intubation may be required following a significant exposure (RMPDC, 1993).
    2) THP CATALEPSY - May be enhanced by scopolamine (Wang & Liu, 1985)
    3) May be diminished by physostigmine (Wang & Liu, 1985)
    D) EXPERIMENTAL THERAPY
    1) NALOXONE - THP is not active at opiate receptors, and is not antagonized by naloxone (Ding, 1987). Naloxone has been used after acute overdose without any apparent effect (Horowitz et al, 1993).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Enhanced Elimination

    A) LACK OF DATA
    1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.

Range Of Toxicity

Summary

    A) OVERDOSE DATA
    1) PEDIATRIC - Three children ingested between 7 and 60 tablets of Jin Bu Huan containing 36% levo tetrahydropalmatine and developed CNS, cardiovascular, and respiratory depression. The children developed no permanent sequelae.
    2) ADULTS - Two adults ingested between 60 to 75 sleeping pills containing approximately 25 milligrams/tablet (approximate dose 1500 to 1875 milligrams) of tetrahydropalmatine, and developed initial central nervous system depression; long term sequelae was NOT reported.
    B) ANIMAL DATA
    1) CATS - An intravenous 40 milligram/kilogram dose slightly dropped blood pressure and heart rate, but did not affect cardiac function significantly.
    2) RABBITS - Doses of 20 to 40 milligrams/kilogram intravenously provided a transient respiratory stimulation, while 60 milligrams/kilogram intravenously depressed respiration.

Therapeutic Dose

    7.2.1) ADULT
    A) SPECIFIC SUBSTANCE
    1) Tetrahydropalmitine - the estimated recommended dose per day is 60 to 480 milligrams (Lai & Chan, 1999).
    2) Corydalis Root - The dose of THP (racemic form) in Chinese medicine is about 60 to 100 milligrams subcutaneously per dose for pain, and 100 to 200 milligrams orally for insomnia (at bedtime) (deSmet et al, 1989) Ding, 1987).
    3) Stephania Root - Tablets are prepared from the Stephania species, which contain the levorotatory form of THP. As an analgesic each tablet contains 60 to 100 milligrams given 1 to 4 times/day (deSmet et al, 1989).

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The minimum lethal human dose to this agent has not been delineated.

Maximum Tolerated Exposure

    A) CASE REPORTS
    1) PEDIATRIC
    a) Three children ingested between 7 and 60 tablets of Jin Bu Huan tablets containing 36% levo tetrahydropalmatine. Rapid development of CNS, cardiovascular, and respiratory depression was observed (RMPDC, 1993). Following supportive care and decontamination the children were alert and responsive within 10 hour or less; no permanent sequelae was reported in any case (Horowitz et al, 1993).
    2) ADULT
    a) Two adults ingested between 60 and 75 sleeping pills which contained approximately 25 milligrams/tablet (approximate dose 1500 to 1875 milligrams) of tetrahydropalmatine, and developed initial central nervous system depression; long term sequelae was NOT reported (Lai & Chan, 1999).
    B) ANIMAL DATA
    1) CATS - An intravenous 40 milligram/kilogram dose slightly dropped blood pressure and heart rate, but did not affect cardiac function significantly (Chang & But, 1986).
    2) RABBITS - Doses of 20 to 40 milligrams/kilogram intravenously provided a transient respiratory stimulation, while 60 milligrams/kilogram intravenously depressed respiration (Chang & But, 1986).
    3) RATS - Single intragastric dose of 85 to 100 milligrams/kilogram did not produce toxicity. An intragastric dose of 180 milligrams/kilogram produced transient respiratory stimulation followed by severe CNS depression. Multiple doses of 85 milligrams/kilogram produced sedation and hypnosis (Chang & But, 1986).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) D,L-TETRAHYDROPALMATINE
    B) D-TETRAHYDROPALMATINE
    C) L-TETRAHYDROPALMATINE
    D) METHYLTETRAHYDROPALMATINE BROMIDE

Pharmacology Toxicology

Pharmacologic Mechanism

    A) The primary mechanism of action of these agents is as a dopamine receptor antagonist. With the levo form, the presynaptic effect is greater than the postsynaptic effect. The dextro form causes inhibition of central dopamine activity (deSmet et al, 1989). Effectively, d-THP is a dopamine depletor, while l-THP is a brain dopamine antagonist (Xu et al, 1987).
    1) Stepholidine and scoulerine have the highest affinity for dopamine receptors. THP is thought to have affinity for both D1 and D2 receptors (Jin, 1987).
    B) Tetrahydropalmatine, as well as other members of this chemical group are naloxone resistant (Jin, 1987).
    C) Both levorotary and racemic possesses sedative, tranquilizing, and analgesic properties in laboratory experiments (Hsu & Kin, 1962) Kin et al, 1984).

Physicochemical

Physical Characteristics

    A) Crystalline (Budavari, 1996)

Molecular Weight

    A) L-TETRAHYDROPALMATINE: 355.47 (RTECS , 2001)
    B) HYDROCHLORIDE SALT: 391.93 (RTECS , 2001)

Animal Toxicology

Clinical Effects

    11.1.6) FELINE/CAT
    A) Intraperitoneal injection of 30 to 80 mg/kg of l-tetrahydropalmatine eliminated deep slow-wave sleep, paradoxical sleep, and pontogeniculo-occipital discharges. Excitation lasting 12 to 30 hours was seen at 80 mg/kg (Ding, 1987).
    11.1.13) OTHER
    A) OTHER
    1) Animals experience CNS depression after ingestion of tetrahydropalmatine (Chang & But, 1986).

Treatment

    11.2.1) SUMMARY
    A) GENERAL TREATMENT
    1) Supportive care only. No specific antidote.

Range Of Toxicity

    11.3.2) MINIMAL TOXIC DOSE
    A) CAT
    1) A 40 milligram per kilogram dose slightly dropped blood pressure and heart rate, but did not affect cardiac function significantly (Chang & But, 1986).
    B) RABBIT
    1) Doses of 20 to 40 milligrams per kilogram provided a transient respiratory stimulation, while 60 milligrams per kilogram depressed respiration (Chang & But, 1986).
    C) RODENT
    1) RATS - Single intragastric dose of 85 to 100 milligrams per kilogram did not produce toxicity. An intragastric dose of 180 milligrams per kilogram produced transient respiratory stimulation followed by severe CNS depresssion. Multiple doses of 85 milligrams per kilogram produced sedation and hypnosis (Chang & But, 1986).

Continuing Care

    11.4.1) SUMMARY
    11.4.1.2) DECONTAMINATION/TREATMENT
    A) GENERAL TREATMENT
    1) Supportive care only. No specific antidote.

References

General Bibliography

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