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Yohimbine

1. NAME
   1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Identification numbers
      1.4.1 CAS number
      1.4.2 Other numbers
   1.5 Brand names, Trade names
   1.6 Manufacturers, Importers
   1.7 Presentation, Formulation
2. SUMMARY
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Diagnosis
   2.4 First aid measures and management principles
3. PHYSICO-CHEMICAL PROPERTIES
   3.1 Origin of the substance
   3.2 Chemical structure
   3.3 Physical properties
      3.3.1 Properties of the substance
         3.3.1.1 Colour
         3.3.1.2 State/Form
         3.3.1.3 Description
      3.3.2 Properties of the locally available formulation
   3.4 Other characteristics
      3.4.1 Shelf-life of the substance
      3.4.2 Shelf-life of the locally available formulation(s)
      3.4.3 Storage conditions
      3.4.4 Bioavailability
      3.4.5 Specific properties and composition
4. USES
   4.1 Indications
      4.1.1 Indications
      4.1.2 Description
   4.2 Therapeutic dosage
      4.2.1 Adults
      4.2.2 Children
   4.3 Contraindications
5. ROUTES OF ENTRY
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Other
6. KINETICS
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life by route of exposure
   6.4 Metabolism
   6.5 Elimination by route of exposure
7. PHARMACOLOGY AND TOXICOLOGY
   7.1 Mode of action
      7.1.1 Toxicodynamics
      7.1.2 Pharmacodynamics
   7.2 Toxicity
      7.2.1 Human data
         7.2.1.1 Adults
         7.2.1.2 Children
      7.2.2 Relevant animal data
      7.2.3 Relevant in vitro data
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
   7.7 Main adverse effects
8. TOXICOLOGICAL AND BIOMEDICAL INVESTIGATIONS
   8.1 Material sampling plan
      8.1.1 Sampling and specimen collection
         8.1.1.1 Toxicological analyses
         8.1.1.2 Biomedical analyses
         8.1.1.3 Arterial blood gas analysis
         8.1.1.4 Haematological analyses
         8.1.1.5 Other (unspecified) analyses
      8.1.2 Storage of laboratory samples and specimens
         8.1.2.1 Toxicological analyses
         8.1.2.2 Biomedical analyses
         8.1.2.3 Arterial blood gas analysis
         8.1.2.4 Haematological analyses
         8.1.2.5 Other (unspecified) analyses
      8.1.3 Transport of laboratory samples and specimens
         8.1.3.1 Toxicological analyses
         8.1.3.2 Biomedical analyses
         8.1.3.3 Arterial blood gas analysis
         8.1.3.4 Haematological analyses
         8.1.3.5 Other (unspecified) analyses
   8.2 Toxicological analyses and their interpretation
      8.2.1 Tests on toxic ingredient(s) of material
         8.2.1.1 Simple qualitative test(s)
         8.2.1.2 Advanced qualitative confirmation test(s)
         8.2.1.3 Simple quantitative method(s)
         8.2.1.4 Advanced quantitative method(s)
      8.2.2 Tests for biological specimens
         8.2.2.1 Simple qualitative test(s)
         8.2.2.2 Advanced qualitative confirmation test(s)
         8.2.2.3 Simple quantitative method(s)
         8.2.2.4 Advanced quantitative method(s)
         8.2.2.5 Other dedicated method(s)
      8.2.3 Interpretation of toxicological
   8.3 Biomedical investigations and their interpretation
      8.3.1 Biochemical analysis
         8.3.1.1 Blood, plasma or serum
         8.3.1.2 Urine
         8.3.1.3 Other fluids
      8.3.2 Arterial blood gas analyses
      8.3.3 Haematological analyses
   8.4 Other biomedical (diagnostic) investigations and their interpretation
   8.5 Overall interpretation of all toxicological analyses and toxicological investigations
   8.6 References
9. CLINICAL EFFECTS
   9.1 Acute poisoning
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure
      9.1.6 Other
   9.2 Chronic poisoning
      9.2.1 Ingestion
      9.2.2 Inhalation
      9.2.3 Skin exposure
      9.2.4 Eye contact
      9.2.5 Parenteral exposure
      9.2.6 Other
   9.3 Course, prognosis, cause of death
   9.4 Systematic description of clinical effects
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurological
         9.4.3.1 Central nervous system (CNS)
         9.4.3.2 Peripheral nervous system
         9.4.3.3 Autonomic nervous system
         9.4.3.4 Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary
         9.4.6.1 Renal
         9.4.6.2 Others
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eye, ears, nose, throat: local effects
      9.4.10 Haematological
      9.4.11 Immunological
      9.4.12 Metabolic
         9.4.12.1 Acid-base disturbances
         9.4.12.2 Fluid and electrolyte disturbances
         9.4.12.3 Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Other
   9.6 Summary
10. MANAGEMENT
   10.1 General principles
   10.2 Relevant laboratory analyses
      10.2.1 Sample collection
      10.2.2 Biomedical analysis
      10.2.3 Toxicological analysis
   10.3 Life supportive procedures and symptomatic/specific treatment
   10.4 Decontamination
   10.5 Elimination
   10.6 Antidote treatment
      10.6.1 Adults
      10.6.2 Children
   10.7 Management discussions
11. ILLUSTRATIVE CASES
   11.1 Case reports from literature
   11.2 Internally extracted data on cases
   11.3 Internal cases
12. ADDITIONAL INFORMATION
   12.1 Availability of antidotes
   12.2 Specific preventive measures
   12.3 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES)
    1. NAME

       1.1 Substance

           Yohimbine

       1.2 Group

           ATC classification index

           All other therapeutic products (V03)/Other therapeutic 
           products (V03AX).

           (WHO, 1992)

       1.3 Synonyms

           Aphrodine Hydrochloride
           Chlorhydrate de Québrachine
           Corynine Hydrochloride
           Yo Yo
           
           (Reynolds, 1993)

       1.4 Identification numbers

           1.4.1 CAS number
         
                 Yohimbine                146-48-5
                 Yohimbine Hydrochloride  65-19-0

           1.4.2 Other numbers

                 RTECS

                 Yohimbine                ZG1000000

       1.5 Brand names, Trade names

           Monocomponent products

           Actibine, Aphrodyne, Dayto Himbin, Revervyl, Reverzine, 
           Yobine, Yocon, Yohimex, Yohydrol 

           Combination products 

           Afrodex, Ictho-Himbin, Pasuma, Pluriviron, Potensan, Potensan 
           Forte, Prowess, Vikonon 

           (To be completed by each Centre using local data) 

       1.6 Manufacturers, Importers 

           To be completed by each Centre using local data

       1.7 Presentation, Formulation

           Tablets, either as single ingredient or in combination with 
           other ingredients, for human use. 

           Sterile injectable solution for veterinary use.

           Street drug (as a powder)

           (To be completed by each Centre using local data)

    2. SUMMARY

       2.1 Main risks and target organs

           Yohimbine is a centrally acting alpha-2-adrenoceptor blocking 
           agent. It may also interact with alpha-1-adrenoceptors and, 
           in high concentrations, serotonin and dopamine receptors. 
           Yohimbine is a monoamine oxidase inhibitor, and has the 
           potential to interact with tyramine-containing foods and 
           stimulants such as phenylephrine and phenylpropanolamine. 

           Yohimbine affects the gastrointestinal, genito-urinary, 
           respiratory, cardiovascular and central nervous systems. 

       2.2 Summary of clinical effects

           Yohimbine produces cardiovascular effects, including 
           increases in heart rate and blood pressure. 

           Bronchospasm and increased mucous secretion has been 
           reported. 

           CNS effects include anxiety, hallucinations and manic 
           reactions. 

           Gastrointestinal effects include nausea, anorexia and 
           diarrhoea. 

           Dysuria, and back and genital pain have occurred. 

           Yohimbine has been used for its alleged aphrodisiac 
           properties but evidence of such an effect is lacking. 

       2.3 Diagnosis 

           There are no significant signs or symptoms which are a key to 
           clinical diagnosis. 

           Qualitative tests are available, and include Thin Layer 
           Chromatography and Gas Chromatography. 

           Although yohimbine may be quantified in the plasma by HPLC, 
           toxic levels have not yet been established. 

       2.4 First aid measures and management principles 

           Support respiratory and cardiovascular function. Emesis may 
           be indicated for substantial ingestions, especially if 
           initiated within 30 minutes of ingestion. Activated charcoal 
           may also be administered. Diazepam may be useful in reducing 
           anxiety. 

    3. PHYSICO-CHEMICAL PROPERTIES

       3.1 Origin of the substance 

           Yohimbine is the principal indole alkaloid derived from the 
           bark of the Yohimbe Tree (Pausinystalia yohimbe = Corynanthe 
           yohimbi) (Rubiaceae). It is also found in the Rauwolfia root 
           and the dried bark of Aspidosperma quebracho. 

           (Reynolds, 1993) 

       3.2 Chemical structure 

           Structural formula 
           
           Molecular formula

           Yohimbine         C21H26N2O3 
           
           Yohimbine         C21H26N2O3,HCl
           Hydrochloride
           
           Molecular weight

           Yohimbine         354.4

           Yohimbine         390.9
           Hydrochloride
           
           Structural Chemical names

           Methyl 17alpha-hydroxy-yohimban-16alpha-carboxylate 
           hydrochloride. 

           (16alpha, 17alpha)-17-Hydroxyyohimban-16-carboxylic acid 
           methyl ester. 

           (Reynolds, 1993; Budavari, 1989)

       3.3 Physical properties

           3.3.1 Properties of the substance

                 3.3.1.1 Colour

                         No data available

                 3.3.1.2 State/Form

                          Yohimbine Hydrochloride

                         Orthorhombic plates
                         Prisms from alcohol
    
                          Yohimbine

                         Orthorhombic needles

                 3.3.1.3 Description

                          Yohimbine Hydrochloride

                         Decomposes at 302 °C
                      
                         Soluble 1 in 120 of water and 1 in 400 of 
                         alcohol
                      
                         Aqueous solution pH    approximately neutral

                          Yohimbine

                         Melting point 234 °C
                      
                         Very slightly soluble in water
                         Soluble in ethanol and chloroform
                         Sparingly soluble in ether

           3.3.2 Properties of the locally available formulation 

                 To be completed by each Centre using local data.

       3.4 Other characteristics

           Store in a cool place. Do not freeze. Protect from light. 

           3.4.1 Shelf-life of the substance

                 No data available.

           3.4.2 Shelf-life of the locally available formulation(s) 

                 To be completed by each Centre using local data.

           3.4.3 Storage conditions
         
                 Store in a cool place. Do not freeze. Protect from 
                 light. 

           3.4.4 Bioavailability

                 To be completed by each Centre using local data.

           3.4.5 Specific properties and composition 

                 To be completed by each Centre using local data. 

    4. USES

       4.1 Indications

           4.1.1 Indications

                 In humans, yohimbine has been used for the treatment of 
                 impotence. 

                 In street use, Yohimbine has been misused as a mild 
                 hallucinogen, and as an aphrodisiac. 

                 As a veterinary preparation, yohimbine is used to 
                 reverse xylazine-induced anaesthesia in animals 
                 including deer, steers, dogs, cats and horses. 

           4.1.2 Description 

                 Not relevant 

       4.2 Therapeutic dosage 

           4.2.1 Adults 

                  Oral 

                 0.1 mg/kg may produce stimulant effects. 

                 6 mg  three times daily has been used to treat 
                 impotence. 

                 Yohimbine has been given in doses up to 30 mg daily 
                 (Moffat, 1986) and the German Pharmacopoeia states a 
                 human dose of up to 100 mg/day (Dukes, 1988). 

           4.2.2 Children

                 No data available.

       4.3 Contraindications

           Yohimbine should not be used in cardiac, hepatic and renal 
           disease. It is a monoamine oxidase inhibitor, therefore 
           tyramine-containing foods and stimulants such as 
           phenylephrine and phenylpropanolamine should be avoided. 

    5. ROUTES OF ENTRY 

       5.1 Oral 

           Most common in humans. 

       5.2 Inhalation 

           The powdered street drug may be smoked. 

       5.3 Dermal 

           No data available. 

       5.4 Eye 

           No data available. 

       5.5 Parenteral 

           Yohimbine has been administered intravenously in clinical 
           research. 

           Accidental injection may occur, especially inveterinary 
           practice. 

       5.6 Other 

           No data available. 

    6. KINETICS

       6.1 Absorption by route of exposure 

           The kinetic disposition of yohimbine was examined in 8 young 
           male subjects following a single oral dose of 10 mg yohimbine 
           hydrochloride. Oral absorption was rapid, with an oral 
           absorption half-life of 0.17 +/- 0.11 hours (approximately 11 
           minutes)(Owen et al, 1987). In a similar study the absorption 
           half-life was approximately 7 minutes (Guthrie et al., 1990). 

           Absorption is complete and peak plasma levels occur at 45 to 
           60 minutes after 10 mg orally (Owen et al, 1987; Guthrie et 
           al., 1990). The bioavailability showed a great variability, 
           ranging from 7 to 87% (Guthrie et al., 1990). 

       6.2 Distribution by route of exposure 

           Oral 

           Studies on the volume of distribution showed a very wide 
           range (mean 2.4 +/- 1.25 L/kg (Owen et al., 1987). 

           Parenteral 

           Rapid distribution phase after intravenous injection of 10 
           mg, alpha half-life approximately 6 minutes. Volume of 
           distribution was small (mean 0.26 L/kg) (Guthrie et al., 
           1990). 

       6.3 Biological half-life by route of exposure 

           Yohimbine was rapidly eliminated from the plasma in 8 young 
           male patients receiving a single 10 mg dose of yohimbine 
           (half-life was 0.60 +/- 0.26 hours) (Owen et al., 1987).  

           After 10 mg yohimbine intravenously, half-life (beta) was 
           0.68 +/- 0.2 hours (Guthrie et al., 1990). 

       6.4 Metabolism 

           Since yohimbine is stable in blood, the rapid clearance of 
           yohimbine from human plasma suggests metabolism of the drug 
           by an organ with high blood flow, such as liver or kidney, 
           and a high extraction efficiency (Owen et al., 1987). 

           Ho et al. (1971) suggest that in mice the rapid metabolism of 
           yohimbine is primarily due to the hydrolysis of the 16-alpha 
           carboxylic acid methyl ester bond to yield yohimbinic acid. 
           However, the hydrolysis of yohimbine to yohimbinic acid is 
           unlikely to be a major metabolic route in humans. This is 
           based on data obtained from pharmacokinetic studies on 
           reserpine and raubasine, two indole alkaloids structurally 
           related to yohimbine. 

           Although both reserpine and raubasine contain a 16-alpha 
           carboxylic acid methyl ester moiety, de-esterification of 
           this group does not appear to be a significant metabolic 
           route for reserpine, and is not a rapid route for elimination 
           for raubasine in humans (Owen et al., 1987). 

       6.5 Elimination by route of exposure 

           Oral 

           Clearance after 10 mg yohimbine 

            Range      2.81 to 200 mL/min/kg 
            Mean              55.9 mL/min/kg 

           Less than 1% of unchanged drug was recovered in the urine in 
           24 hours. 

           (Owen et al., 1987).

           Parenteral

           Clearance after 10 mg yohimbine intravenously

            Range     2.44 to 15.8 mL/min/kg
            Mean              9.77 mL/min/kg

    7. PHARMACOLOGY AND TOXICOLOGY

       7.1 Mode of action

           Yohimbine is a competitive antagonist selective for alpha 
           2-andrenoceptors, which are thought to be located on nerve 
           terminals and receptors and to mediate inhibition of 
           transmitter release. The presynaptic release of noradrenaline 
           is increased by an alpha-2-antagonist resulting in increased 
           sympathetic outflow. Yohimbine may also interact with alpha-
           1-adrenoceptors and, in high concentrations, serotonin and 
           dopamine receptors (Dukes, 1988). Yohimbine has monoamine 
           oxidase inhibitory effects (Bhattacharya et al., 1991). 

           7.1.1 Toxicodynamics 

                 It has been suggested that a central beta-origin 
                 toxicity exists, since only beta blockers which cross 
                 the blood-brain barrier are capable of antagonizing 
                 this activity (Bourin et al., 1988). 

           7.1.2 Pharmacodynamics 

                 Yohimbine is an alpha-2-adrenergic antagonist. It 
                 increases the heart rate and blood pressure and causes 
                 CNS stimulation and anti-diuresis (Reynolds et al., 
                 1989). 

       7.2 Toxicity 

           7.2.1 Human data 

                 7.2.1.1 Adults 

                         An ingested dose of 1.8 g (100 times the 
                         average daily dose) resulted in unconsciousness 
                         for some hours, with priapism. The patient 
                         recovered fully within a few days (Roth et al., 
                         1984; as cited in Dukes, 1988). 

                 7.2.1.2 Children 

                         No data available. 

           7.2.2 Relevant animal data 

                 LD50  Oral (mouse)            43 mg/kg 
                 LDLO  Intravenous (mouse)     16 mg/kg 
                 LDLO  Intravenous (rabbit)    11 mg/kg 
                 LD50  Subcutaneous (mouse)    20 mg/kg 
                 LDLO  Subcutaneous (rabbit)   50 mg/kg 

                 (RTECS,1987)

           7.2.3 Relevant in vitro data

                 No data available.

       7.3 Carcinogenicity

           No data available.

       7.4 Teratogenicity

           No data available.

       7.5 Mutagenicity

           No data available.

       7.6 Interactions

           Yohimbine has monoamine oxidase inhibitory effects, and
           thus has the potential to interact with tyramine-containing
           foods and stimulants such as phenylephrine and
           phenylpropanolamine (Bhattacharya et al., 1991).

       7.7 Main adverse effects

           Principal adverse effects to be expected in humans with the
           use of moderate doses are emotional arousal and a rise in
           blood pressure and heart rate. An oral dose of 6 mg three
           times per day resulted in only minimal adverse effects such
           as dizziness and nervousness (Dukes, 1988).

    8. TOXICOLOGICAL AND BIOMEDICAL INVESTIGATIONS

       8.1 Material sampling plan

           8.1.1 Sampling and specimen collection

                 8.1.1.1 Toxicological analyses
                 8.1.1.2 Biomedical analyses
                 8.1.1.3 Arterial blood gas analysis
                 8.1.1.4 Haematological analyses
                 8.1.1.5 Other (unspecified) analyses

           8.1.2 Storage of laboratory samples and specimens

                 8.1.2.1 Toxicological analyses
                 8.1.2.2 Biomedical analyses
                 8.1.2.3 Arterial blood gas analysis
                 8.1.2.4 Haematological analyses
                 8.1.2.5 Other (unspecified) analyses

           8.1.3 Transport of laboratory samples and specimens
         
                 8.1.3.1 Toxicological analyses
                 8.1.3.2 Biomedical analyses

                 8.1.3.3 Arterial blood gas analysis
                 8.1.3.4 Haematological analyses
                 8.1.3.5 Other (unspecified) analyses

       8.2 Toxicological analyses and their interpretation

           8.2.1 Tests on toxic ingredient(s) of material

                 8.2.1.1 Simple qualitative test(s)

                         Colour tests: Liebermann's Test - blue
                                         Mandelin's Test - blue > green

                 8.2.1.2 Advanced qualitative confirmation test(s)

                         Thin-Layer Chromatography: system TA-Rf 63; 
                         system TB-Rf 05; system TC-Rf 38 (Dragendorff 
                         spray, positive; acidified iodoplatinate 
                         solution, positive; Marquis Reagent, grey). 

                         Gas Chromatography: system GA-RI 3296. 

                 8.2.1.3 Simple quantitative method(s) 

                 8.2.1.4 Advanced quantitative method(s) 

                         High Pressure Liquid Chromatography. In plasma: 
                         sensitivity 10 ng/mL, electrochemical 
                         detection. 

           8.2.2 Tests for biological specimens

                 8.2.2.1 Simple qualitative test(s)
                 8.2.2.2 Advanced qualitative confirmation test(s)
                 8.2.2.3 Simple quantitative method(s)
                 8.2.2.4 Advanced quantitative method(s)
                 8.2.2.5 Other dedicated method(s)

           8.2.3 Interpretation of toxicological

       8.3 Biomedical investigations and their interpretation

           No specific laboratory test are necessary unless clinically 
           indicated. 
         
           8.3.1 Biochemical analysis
         
                 8.3.1.1 Blood, plasma or serum
                         "Basic analyses"
                         "Dedicated analyses"
                         "Optional analyses"
                 8.3.1.2 Urine
                         "Basic analyses"
                         "Dedicated analyses"
                         "Optional analyses"

                 8.3.1.3 Other fluids

           8.3.2 Arterial blood gas analyses
           8.3.3 Haematological analyses
                 "Basic analyses"
                 "Dedicated analyses"
                 "Optional analyses"

       8.4 Other biomedical (diagnostic) investigations and their
           interpretation

       8.5 Overall interpretation of all toxicological analyses and 
           toxicological investigations 

       8.6 References

           Goldberg MR et al. (1984) J Liq Chromat, 7: 1003-1004.
    
    9. CLINICAL EFFECTS

       9.1 Acute poisoning 

           9.1.1 Ingestion

                 Fatalities resulting from acute overdosage of yohimbine 
                 have not been reported. Signs of overdosage include CNS 
                 depression, ranging from drowsiness to coma. 
                 Respiratory depression, hypothermia, diarrhoea, 
                 vomiting, mental depression, flushing of the skin, 
                 hypertension, cardiac arrhythmias, tachycardia and 
                 short-term reversible paraesthesias of the legs and 
                 feet may occur. 

           9.1.2 Inhalation 

                 Mild hallucinations, including a disassociative state, 
                 can occur when yohimbine is smoked (Linden et al., 
                 Siegel, 1976). 

           9.1.3 Skin exposure 

                 Not relevant. 

           9.1.4 Eye contact 

                 No data available. 

           9.1.5 Parenteral exposure 

                 Symptoms would be as for those listed in Section 9.1.1 
                 (Ingestion). 
         
           9.1.6 Other 

                 No data available. 

       9.2 Chronic poisoning 

           9.2.1 Ingestion 

                 No data available. 

           9.2.2 Inhalation 

                 No data available. 

           9.2.3 Skin exposure 

                 No data available. 

           9.2.4 Eye contact 

                 No data available. 

           9.2.5 Parenteral exposure 

                 No data available. 

           9.2.6 Other 

                 No data available. 

       9.3 Course, prognosis, cause of death 

           Fatalities resulting from acute overdosage of yohimbine have 
           not been reported. Large overdoses may impair cardiac 
           function and cause CNS depression, including coma. 

       9.4 Systematic description of clinical effects 

           9.4.1 Cardiovascular 

                 Tachycardia, atrial fibrillation and hypertension are 
                 features of yohimbine toxicity. Systolic blood pressure 
                 increased significantly in subjects given oral doses of 
                 yohimbine. The differences for diastolic pressure were 
                 not significant (Henauer et al., 1984). 

                 Patients with orthostatic hypotension appear to be very 
                 sensitive to the effects of yohimbine. A 5 mg dose may 
                 increase blood pressure, while greater than 20 mg is 
                 needed in a healthy volunteer (to raise the blood 
                 pressure 40 mmHg systolic)(Brosse et al., 1983). 

           9.4.2 Respiratory 

                 Bronchospasm and increased mucous secretion have been 
                 reported (Landis & Shore, 1989). 

           9.4.3 Neurological 

                 9.4.3.1 Central nervous system (CNS) 

                         Dizziness, insomnia, headache and irritability 
                         have been reported (Goldberg & Robertson, 
                         1983). 

                         Yohimbine produced manic reactions in bipolar 
                         psychiatric patients. Symptoms included 
                         tremulousness, restlessness, giddiness, rapid 
                         speech, laughing, increased energy and euphoria 
                         (Price et al., 1984). 

                         Mild hallucinations, including a disassociative 
                         state, can occur when yohimbine is smoked or 
                         used in a tea (Linden et al, 1985; Siegel, 
                         1976). 

                         Inco-ordination was observed following abuse of 
                         yohimbine (Linden et al., 1985). It is commonly 
                         reported to cause anxiety (Charney et al., 
                         1983). 

                 9.4.3.2 Peripheral nervous system 

                         Short-term reversible paraesthesias of the legs 
                         and feet were reported in diabetics being 
                         treated for impotency and in overdoses (Morales 
                         et al., 1982; Linden et al., 1985). 

                 9.4.3.3 Autonomic nervous system 

                         Not relevant 

                 9.4.3.4 Skeletal and smooth muscle 

                         Not relevant 

           9.4.4 Gastrointestinal 

                 Nausea, vomiting, diarrhoea and anorexia have been 
                 reported (Goldberg & Robertson, 1983). 

           9.4.5 Hepatic 

                 No data available. 

           9.4.6 Urinary 
                      
                 9.4.6.1 Renal 

                         Dysuria has been reported (Goldberg & 
                         Robertson, 1983). 

                 9.4.6.2 Others 

                         Genital pain has been reported (Goldberg & 
                         Robertson, 1983). 

           9.4.7 Endocrine and reproductive systems 

                 Studies have shown yohimbine to be 3 to 3.4 times as 
                 effective as placebo in relieving male impotency 
                 (Sobotka, 1969). 

           9.4.8 Dermatological 

                 Not relevant 

           9.4.9 Eye, ears, nose, throat: local effects 

                 No data available. 

           9.4.10 Haematological 

                  No data available. 

           9.4.11 Immunological 

                  No data available. 

           9.4.12 Metabolic 

                  9.4.12.1 Acid-base disturbances 

                           No data available. 

                  9.4.12.2 Fluid and electrolyte disturbances 

                           No data available. 

                  9.4.12.3 Others 

                           Yohimbine is a monoamine oxidase inhibitor, 
                           and thus has the potential for reacting with 
                           tyramine-containing foods. 
                
           9.4.13 Allergic reactions 

                  No data available. 

           9.4.14 Other clinical effects 

                  No data available. 

           9.4.15 Special risks 

                  No data available. 
            
       9.5 Other 

           No data available. 

       9.6 Summary 

           Not relevant 

    10. MANAGEMENT

        10.1 General principles 

             Treatment is symptomatic and supportive, including 
             maintaining respiratory and cardiovascular function. 

        10.2 Relevant laboratory analyses 

             10.2.1 Sample collection 

                    Not relevant 

             10.2.2 Biomedical analysis 

                    No specific analyses unless clinically indicated. 

             10.2.3 Toxicological analysis 

                    Qualitative tests are available, and include Thin 
                    Layer Chromatography and Gas Chromatography. 

                    Although yohimbine may be quantified in the plasma 
                    by HPLC, toxic levels have not yet been established. 

        10.3 Life supportive procedures and symptomatic/specific 
             treatment 

             Support respiratory and cardiovascular function. 

             Diazepam has been shown to be useful in treating yohimbine-
             induced anxiety. Dose is given either orally or by slow 
             intravenous injection: 
            
              Adult     5 to 10 mg 
              Child     0.1 - 0.3 mg/kg bodyweight 

             If priapism is prolonged (more than 4 hours) then specific 
             treatment may be required, e.g. aspiration of the corpus 
             may be required. 

        10.4 Decontamination
            
             Emesis should be considered following recent ingestion of 
             amounts exceeding the maximum therapeutic dose or if there 
             is evidence of any overdose, if the patient is not 

             comatose, is not convulsing, and has not lost the gag 
             reflex. 

             Where emesis is contraindicated, gastric lavage should be 
             considered. 

             Administer activated charcoal orally (adults 50 g; children 
             1 g/kg). 
         
        10.5 Elimination 

             No data available. 

        10.6 Antidote treatment 
            
             10.6.1 Adults 

                    Clonidine has been used experimentally as an 
                    antidote in normal volunteers to eliminate 
                    yohimbine-induced anxiety (see Section 10.7). 

             10.6.2 Children 

                    No data available 

        10.7 Management discussions 

             Clonidine 5 micrograms/kg bodyweight was found to eliminate 
             not only yohimbine-induced anxiety but also the increases 
             in blood pressure, plasma MHPG, and other autonomic 
             symptoms in a study using normal volunteers who ingested 
             30 mg yohimbine. However, before clonidine can be 
             recommended as a routine antidote for yohimbine toxicity, 
             further clinical evaluation is required (Charney et al., 
             1983). 

    11. ILLUSTRATIVE CASES 

        11.1 Case reports from literature 

             Case 1 

             An ingested dose of 1.8 g yohimbine (100 times the average 
             daily rate) resulted in unconsciousness for some hours with 
             priapism. The patient recovered fully within a few days 
             (Roth et al., 1984; as cited in Dukes, 1988). 

             Case 2 
    
             A 38-year-old man with insulin dependent diabetes was 
             admitted two hours after taking 350 mg yohimbine. The drug 
             had been prescribed by a consultant psychiatrist for 
             erectile impotence complicated by depression. 

             On admission to hospital he was alert and oriented. His 
             blood pressure was 130/80 mmHg and his pulse was regular at 
             88 beats/minute. Six hours after admission he discharged 
             himself, but was readmitted 17 hours later in a drowsy and 
             confused state. He was having rigors and complained of 
             retrosternal pain. He did not appear to have taken any 
             other drug. His rectal temperature as 35.5°C and his blood 
             pressure was 135/85 mmHg. His hands and feet were warm and 
             well-perfused. Blood urea was 12.8 mmol/L, serum creatine 
             175 umol/L, and blood glucose 16.7 mmol/L. An electro-
             cardiogram showed atrial fibrillation with a ventricular 
             rate of 150 beats/minute. The day after admission an 
             electrocardiogram showed sinus rhythm, and retrograde 
             amnesia for the preceding 24 hours persisted for four days. 

             Case 3 

             A 16-year-old female took an estimated 250 mg of a white 
             powder alleged to be yohimbine. Within 20 minutes she was 
             weak, had generalized paraesthesia, loss of coordination, 
             and was disassociative. She had a severe headache, was 
             dizzy, and had no tremors. A severe pressure-like 
             substernal chest pain was noted 4 hours post-ingestion, and 
             remained for 2 hours before subsiding spontaneously. The 
             next day, the patient remained weak and dizzy, with nausea, 
             sweating, severe headache and intermittent palpitations. On 
             examination more than 30 hours after ingestion, she had a 
             blood pressure of 150/80, pulse of 116 and respiration rate 
             of 24. She was anxious, with a blotchy erythematous rash on 
             her back and submucosal haemorrhage in the right tympanic 
             membrane. Symptoms resolved spontaneously but had lasted 36 
             hours (Linden et al., 1985). 

        11.2 Internally extracted data on cases 

             No data available.

        11.3 Internal cases

             To be completed by each Centre using local data.

    12. ADDITIONAL INFORMATION

        12.1 Availability of antidotes

             No specific antidote is available (see Section 10.7).

        12.2 Specific preventive measures

             Store in a cool place out of direct sunlight. Keep out of 
             reach of children. 

        12.3 Other

             Not relevant.
             
    13. REFERENCES

        Bhattacharya SK, Clow A, Przuborowska A, Halket J, Glover V, & 
        Sandler M (1991) Effect of aromatic amino acids, 
        pentylenetetrazole and yohimbine on isatin and tribulin activity 
        in rat brain. Neurosci-Lett 28, 132(1): 44-6. 

        Brodd OE, Anlauf M, & Arroyo J (1983) Hypersensitivity of 
        adrenergic receptors and blood pressure response to oral 
        yohimbine in orthostatic hypotension. New Engl J Med, 17: 1033-
        1034. 

        Bourin M, Malinge M, Colombel MC, & Larousse C (1988) Influence 
        of alpha stimulants and beta blockers on yohimbine toxicity. 
        Prog Neuropsychopharmacol Biol Psychiatry, 12: 569-574. 

        Budavari S ed. (1989) The Merck index, an encyclopedia of 
        chemicals, drugs, and biologicals, 11th ed. Rahway, New Jersey, 
        Merck and Co., Inc.  p 1594. 

        Charney DS, Heninger GR, & Redmond DE (1983) Yohimbine -induced 
        anxiety and increased non-adrenergic function in humans: effects 
        of diazepam and clonidine: Life Sci, 33: 19-29. 

        Dukes MNG ed. (1988) Meyler's Side Effect of Drugs. Amsterdam, 
        Elsevier, pp. 1024-1028. 

        Goldberg MR & Robertson D (1983) Yohimbine: a pharmacological 
        probe for study of the alpha-2-adrenoreceptor. Pharmacol Rev, 
        35: 143-180. 

        Guthrie SK, Hariharan M, & Grunhaus LJ (1990) Yohimbine 
        bioavailability in humans. Eur J Clin Pharmacol, 39: 409-411. 

        Henauer SA, Gillespie HK, & Hollister LE (1984) Yohimbine and 
        the model anxiety state. J Clin Psychiatry, 45: 512-515. 

        Ho AKJ, Hoffman DB, Gershon S, & Loh HH (1971) Distribution and 
        metabolism of tritiated yohimbine in mice. Arch Int Pharmacodyn, 
        194: 304-315. 

        Linden CH, Vellman WP, & Rumack B (1985) Yohimbine a new street 
        drug. Am Emerg Med, 14: 1002-1004. 

        Moffat AC ed. (1986) Clarke's isolation and identification of 
        drugs (in pharmaceuticals, body fluids and post-mortem 
        material), 2nd ed., London, Pharmaceutical Press. 

        Morales A, Surridge DHC, Marshall PG , & Fenemore J (1982) Non-
        hormonal pharmacological treatment of organic impotence. J Urol, 
        128(1): 45-47. 

        Owen JA, Nakatsu SL, Fenemore J, Condra M, Surridge DH, & 
        Morales A (1987) The pharmacokinetics of yohimbine in man. Eur J 
        Clin Pharmacol, 32(6): 577-582. 

        Price HL, Charney DS, & Heninger K (1984) Three cases of manic 
        symptoms following Yohimbine administration. Am J Psychiatry, 
        141: 1267-1268. 
        
        Reynolds JEF ed. (1989) Martindale, the extra pharmacopoeia, 
        29th ed. London, The Pharmaceutical Press, p 1630. 
        
        Reynolds JEF ed. (1993) Martindale, the extra pharmacopoeia, 
        30th ed. London, The Pharmaceutical Press, p 1428. 

        Roth L, Daunderer M, & Kormann K (1984) In: Giftplanzen -
        Planzengifte: Vorkommen, Wirkung, Therapie, IV-P, p. 4. 
        Landberg, Munich, Ecomed. 

        RTECS (1987) Registry of Toxic Effects of Chemical Substances. 
        1985-1986 Edition. US Department of Health and Human Services, 
        Public Health Service, Centres for Disease Control, National 
        Institute for Occupational Safety and Health, pp 5132-5133. 

        Siegel RK (1976) Herbal intoxication. Psycho-active effects from 
        herbal cigarettes, tea and capsule. JAMA, 236: 473-376. 

        Sobotka JJ (1969) An evaluation of Afrodex TM in the management 
        of male impotency: a double-blind cross-over study. Curr Ther 
        Res, 2: 87-94. 

        WHO (1992) Anatomical Therapeutic Chemical (ATC) classification 
        index. Oslo, WHO Collaborating Centre for Drug Statistics 
        Methodology, p 106. 
        
    14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE 
        ADDRESS(ES) 

        Authors       Dr Wayne A. Temple 
                      National Toxicology Group 
                      University of Otago Medical School 

                      Dr Nerida A. Smith
                      Pharmacy School
                      University of Otago

                      PO Box 913
                      Dunedin
                      New Zealand

                      Tel:    64-3-4797244
                      Fax:    64-3-4770509

                      Date    July 1992

        Reviewer      Poisons Unit
                      New Cross Hospital
                      Avonley Road
                      London SE14 5ER
                      United Kingdom

                      Tel: 44-71-9555095
                      Fax: 44-71-6392101

                      Date    July 1992
                              
        Peer Review   Drs Deng, Ferner, Landoni, Maramba, Shintani, 
                      Wickstrom. London, July, 1992. 








    See Also:
       Toxicological Abbreviations