Talk:Yohimbine: Difference between revisions

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{{headerpanel|{{Approval}}}}

'''Yohimbine''' hydrochloride (also known as '''quebrachine''') is a [[naturally-occurring]] [[Psychoactive class::stimulant]] substance of the [[chemical class::tryptamine]] class derived from the bark of the African tree ''Pausinystalia johimbe''. ~~Yohimbine~~ is the major active constituent of the bark, with the active ingredient being yohimbine hydrochloride. It ~~is commonly used~~ as a ~~fat-burning compound or for to treatment of erectile dysfunction~~.

'''Yohimbine''' hydrochloride (also known as '''quebrachine''') is a [[naturally-occurring]] [[Psychoactive class::stimulant]] substance of the [[chemical class::tryptamine]] class derived from the bark of the African tree [[wikipedia:Pausinystalia johimbe|''Pausinystalia johimbe'']]. It is the major active constituent of the bark, with the active ingredient being yohimbine hydrochloride. It has various uses including as an aphrodisiac and a weight loss agent. Yohimbine is also used as a mydriatic and sympatholytic and has been suggested as an antidote to [[clonidine]] and [[wikipedia:xylazine|xylazine]] overdose.

Yohimbine is a ~~drug used in veterinary medicine~~ to ~~reverse the effects of~~ [[wikipedia:xylazine|xylazine]] ~~in dogs and deer. It is used as a research reagent. In the US it is prescribed, but now rarely, for erectile dysfunction in men~~.

==Chemistry==

Yohimbine is an indole alkaloid molecule of the [[tryptamine]] chemical class.

==Pharmacology==

~~In low doses yohimbine will~~ antagonize ~~alpha2~~ adrenergic receptors, leading to increased blood flow to the genital area, where blocking the presynaptic ~~alpha2~~ receptors will lead to an increase in both nitric oxide & noradrenaline release. Blocking alpha-2 adrenoceptors increases blood pressure, releases insulin, and decreases blood sugar levels.

Yohimbine antagonize alpha-2 [[adrenergic]] [[receptors]], leading to increased blood flow to the genital area, where blocking the presynaptic alpha-2 receptors will lead to an increase in both nitric oxide and [[noradrenaline]] release. Blocking alpha-2 adrenoceptors increases blood pressure, releases insulin, and decreases blood sugar levels. Yohimbine also, however, interacts with alpha-1 adrenergic receptors, albeit with lower affinity, therefore, at higher doses an α1 blockade can occur and overwhelm the effects of the α2 blockade, making it difficult to predict the response (alpha-1 antagonism reduces blood pressure and overall CNS stimulation). It also has been shown to weak [[MAOI|inhibit monoamine oxidase]].<ref name="Toxic">Encyclopedia of Toxicology | https://www.sciencedirect.com/science/article/pii/B9780123864543007995</ref>

Yohimbine also, however, interacts with ~~alpha1~~ adrenergic receptors, albeit with lower affinity, therefore, at higher doses an α1 blockade can occur and overwhelm the effects of the α2 blockade, making it difficult to predict the response, (~~alpha1~~ antagonism reduces blood pressure and overall CNS stimulation) ~~and it will~~ also ~~influence other receptors~~.

~~Yohimbine~~ behaves as an antagonist at dopamine D2 and D3 receptors, serotonin 5-~~HT1B~~, 5-~~HT1D, 5-HT2A~~, and 5-~~HT2B~~ receptors, and as a partial agonist at 5-~~HT1A~~.<ref>Agonist and antagonist actions of yohimbine as compared to fluparoxan at alpha(2)-adrenergic receptors (AR)s, serotonin (5-HT)(1A), 5-HT(1B), 5-HT(1D) and dopamine D(2) and D(3) receptors. Significance for the modulation of frontocortical monoaminergic transmission and depressive states. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/10611634</ref>

In high concentrations yohimbine behaves as an [[antagonist]] at [[dopamine]] D2 and D3 [[receptors]], [[serotonin]] 5-HT1B, 5-HT1D, and 5-HT2B receptors, and as a partial [[agonist]] at 5-HT1A.<ref>Agonist and antagonist actions of yohimbine as compared to fluparoxan at alpha(2)-adrenergic receptors (AR)s, serotonin (5-HT)(1A), 5-HT(1B), 5-HT(1D) and dopamine D(2) and D(3) receptors. Significance for the modulation of frontocortical monoaminergic transmission and depressive states. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/10611634</ref>

==Subjective effects==

{{effects/base

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*'''[[Effect::Stimulation]]''' - Stimulation is especially noticeable once you begin an activity that increase adrenaline output, such as training.

*'''[[Effect::Appetite suppression]]'''<ref>Yohimbine and rauwolscine reduce food intake of genetically obese (obob) and lean mice. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/6145164</ref>

*'''[[Effect::Dizziness]]'''

*'''[[Effect::Dizziness]]'''<ref name="Toxic"/>

*'''[[Effect::Headaches]]'''

*'''[[Effect::Headaches]]'''<ref name="Toxic"/>

*'''[[Effect::Increased blood pressure]]''' ~~- Small doses can increase blood pressure by causing a relatively selective α2 blockade.~~

*'''[[Effect::Increased blood pressure]]'''<ref name="Biomedical"/>

*'''[[Effect::Decreased blood pressure]]''' ~~- At higher doses an α1 blockade can leading to a drop in blood pressure.~~

*'''[[Effect::Decreased blood pressure]]'''

*'''[[Effect::Increased heart rate]]'''

*'''[[Effect::Increased heart rate]]'''<ref name="Toxic"/>

*'''[[Effect::Increased perspiration]]'''

*'''[[Effect::Stamina enhancement]]'''

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*'''[[Effect::Increased salivation]]'''<ref>Evidence for activation of both adrenergic and cholinergic nervous pathways by yohimbine, an alpha 2-adrenoceptor antagonist. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/7557820</ref>

*'''[[Effect::Tactile enhancement]]'''

*'''[[Effect::Nausea]]'''<ref name="Toxic"/>

*'''[[Effect::Pupil dilation]]'''<ref name="Toxic"/>

*'''[[Effect::Seizures]]''' - In high doses.<ref name="Toxic"/>

*'''[[Effect::Motor control loss|Incoordination]]'''<ref name="Toxic"/>

*'''[[Effect::Frequent urination]]'''<ref name="Biomedical"/>

}}

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*'''[[Effect::Anxiety suppression]]''' - Yohimbine decrease social anxiety and increased mood. <ref>Yohimbine enhancement of exposure therapy for social anxiety disorder: a randomized controlled trial. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/24237691</ref><ref>Cognitive Enhancers for Anxiety Disorders (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114287/</ref>

*'''[[Effect::Analysis enhancement]]'''<ref>Differential effects of noradrenergic drugs on anxiety and arousal in healthy volunteers with high and low anxiety. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/9004342</ref>

*'''[[Effect::Anxiety]]'''

*'''[[Effect::Anxiety]]'''<ref name="Toxic"/>

*'''[[Effect::Increased libido]]'''

*'''[[Effect::Irritability]]'''

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==Toxicity and harm potential==

Yohimbine has a [[Toxicity::low toxicity]] relative to dose. Side effects associated with the use of yohimbine include anxiety, an increased urinary frequency, and increases in blood pressure at higher doses.<ref name="Biomedical">Reference Module in Biomedical Sciences | https://www.sciencedirect.com/science/article/pii/B9780128012383988627</ref> Higher doses (200 – 5,000 mg) result in stronger side effects and can be toxic to the brain. Extremely high doses (above 5,000 mg) can be lethal.<ref>Case study: two fatal case reports of acute yohimbine intoxication. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/23846025</ref>

===Dependence and abuse potential===

Yohimbine may potentially be [[Addiction potential::mildly habit forming]] and the desire to use it may actually ''increase'' with use. However, in comparison to other more traditional [[stimulants]] such as [[amphetamine]] or [[methylphenidate]], it is not nearly as addictive or compulsive.

===Dangerous interactions===

==Legal status==

==See also==

@@ Line 1: / Line 1: @@
-{{Stub}}
+{{headerpanel|{{Approval}}}}
 {{SummarySheet}}
 {{SubstanceBox/Yohimbine}}
-'''Yohimbine''' hydrochloride (also known as '''quebrachine''') is a [[naturally-occurring]] [[Psychoactive class::stimulant]] substance of the [[chemical class::tryptamine]] class derived from the bark of the African tree ''Pausinystalia johimbe''. Yohimbine is the major active constituent of the bark, with the active ingredient being yohimbine hydrochloride. It is commonly used as a fat-burning compound or for to treatment of erectile dysfunction.
+'''Yohimbine''' hydrochloride (also known as '''quebrachine''') is a [[naturally-occurring]] [[Psychoactive class::stimulant]] substance of the [[chemical class::tryptamine]] class derived from the bark of the African tree [[wikipedia:Pausinystalia johimbe|''Pausinystalia johimbe'']]. It is the major active constituent of the bark, with the active ingredient being yohimbine hydrochloride. It has various uses including as an aphrodisiac and a weight loss agent. Yohimbine is also used as a mydriatic and sympatholytic and has been suggested as an antidote to [[clonidine]] and [[wikipedia:xylazine|xylazine]] overdose.
-Yohimbine is a drug used in veterinary medicine to reverse the effects of [[wikipedia:xylazine|xylazine]] in dogs and deer. It is used as a research reagent. In the US it is prescribed, but now rarely, for erectile dysfunction in men.
 ==Chemistry==
+{{chemistry}}
 Yohimbine is an indole alkaloid molecule of the [[tryptamine]] chemical class.
 ==Pharmacology==
-In low doses yohimbine will antagonize alpha2 adrenergic  receptors, leading to increased blood flow to the genital area, where blocking the presynaptic alpha2 receptors will lead to an increase in both nitric oxide & noradrenaline release.  Blocking alpha-2 adrenoceptors increases blood pressure, releases insulin, and decreases blood sugar levels.
+{{pharmacology}}
+Yohimbine antagonize alpha-2 [[adrenergic]] [[receptors]], leading to increased blood flow to the genital area, where blocking the presynaptic alpha-2 receptors will lead to an increase in both nitric oxide and [[noradrenaline]] release.  Blocking alpha-2 adrenoceptors increases blood pressure, releases insulin, and decreases blood sugar levels. Yohimbine also, however, interacts with alpha-1 adrenergic receptors, albeit with lower affinity, therefore, at higher doses an α<sub>1</sub> blockade can occur and overwhelm the effects of the α<sub>2</sub> blockade, making it difficult to predict the response (alpha-1 antagonism reduces blood pressure and overall CNS stimulation). It also has been shown to weak [[MAOI|inhibit monoamine oxidase]].<ref name="Toxic">Encyclopedia of Toxicology | https://www.sciencedirect.com/science/article/pii/B9780123864543007995</ref>
-Yohimbine also, however, interacts with alpha1 adrenergic receptors, albeit with lower affinity, therefore, at higher doses an α1 blockade can occur and overwhelm the effects of the α2 blockade, making it difficult to predict the response, (alpha1 antagonism reduces blood pressure and overall CNS stimulation) and it will also influence other receptors.
-Yohimbine behaves as an antagonist at dopamine D2 and D3 receptors, serotonin 5-HT1B, 5-HT1D, 5-HT2A, and 5-HT2B receptors, and as a partial agonist at 5-HT1A.<ref>Agonist and antagonist actions of yohimbine as compared to fluparoxan at alpha(2)-adrenergic receptors (AR)s, serotonin (5-HT)(1A), 5-HT(1B), 5-HT(1D) and dopamine D(2) and D(3) receptors. Significance for the modulation of frontocortical monoaminergic transmission and depressive states. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/10611634</ref>
+In high concentrations yohimbine behaves as an [[antagonist]] at [[dopamine]] D<sub>2</sub> and D<sub>3</sub> [[receptors]], [[serotonin]] 5-HT<sub>1B</sub>, 5-HT<sub>1D</sub>, and 5-HT<sub>2B</sub> receptors, and as a partial [[agonist]] at 5-HT<sub>1A</sub>.<ref>Agonist and antagonist actions of yohimbine as compared to fluparoxan at alpha(2)-adrenergic receptors (AR)s, serotonin (5-HT)(1A), 5-HT(1B), 5-HT(1D) and dopamine D(2) and D(3) receptors. Significance for the modulation of frontocortical monoaminergic transmission and depressive states. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/10611634</ref>
 ==Subjective effects==
+{{EffectStub}}
 {{Preamble/SubjectiveEffects}}
 {{effects/base
@@ Line 24: / Line 23: @@
 *'''[[Effect::Stimulation]]''' - Stimulation is especially noticeable once you begin an activity that increase adrenaline output, such as training.
 *'''[[Effect::Appetite suppression]]'''<ref>Yohimbine and rauwolscine reduce food intake of genetically obese (obob) and lean mice. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/6145164</ref>
-*'''[[Effect::Dizziness]]'''
+*'''[[Effect::Dizziness]]'''<ref name="Toxic"/>
-*'''[[Effect::Headaches]]'''
+*'''[[Effect::Headaches]]'''<ref name="Toxic"/>
-*'''[[Effect::Increased blood pressure]]''' - Small doses can increase blood pressure by causing a relatively selective α2 blockade.
+*'''[[Effect::Increased blood pressure]]'''<ref name="Biomedical"/>
-*'''[[Effect::Decreased blood pressure]]''' - At higher doses an α1 blockade can leading to a drop in blood pressure.
+*'''[[Effect::Decreased blood pressure]]'''
-*'''[[Effect::Increased heart rate]]'''
+*'''[[Effect::Increased heart rate]]'''<ref name="Toxic"/>
 *'''[[Effect::Increased perspiration]]'''
 *'''[[Effect::Stamina enhancement]]'''
@@ Line 35: / Line 34: @@
 *'''[[Effect::Increased salivation]]'''<ref>Evidence for activation of both adrenergic and cholinergic nervous pathways by yohimbine, an alpha 2-adrenoceptor antagonist. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/7557820</ref>
 *'''[[Effect::Tactile enhancement]]'''
+*'''[[Effect::Nausea]]'''<ref name="Toxic"/>
+*'''[[Effect::Pupil dilation]]'''<ref name="Toxic"/>
+*'''[[Effect::Seizures]]''' - In high doses.<ref name="Toxic"/>
+*'''[[Effect::Motor control loss|Incoordination]]'''<ref name="Toxic"/>
+*'''[[Effect::Frequent urination]]'''<ref name="Biomedical"/>
 }}
@@ Line 40: / Line 44: @@
 *'''[[Effect::Anxiety suppression]]''' - Yohimbine decrease social anxiety and increased mood. <ref>Yohimbine enhancement of exposure therapy for social anxiety disorder: a randomized controlled trial. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/24237691</ref><ref>Cognitive Enhancers for Anxiety Disorders (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114287/</ref>
 *'''[[Effect::Analysis enhancement]]'''<ref>Differential effects of noradrenergic drugs on anxiety and arousal in healthy volunteers with high and low anxiety. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/9004342</ref>
-*'''[[Effect::Anxiety]]'''
+*'''[[Effect::Anxiety]]'''<ref name="Toxic"/>
 *'''[[Effect::Increased libido]]'''
 *'''[[Effect::Irritability]]'''
@@ Line 56: / Line 60: @@
 ==Toxicity and harm potential==
+Yohimbine has a [[Toxicity::low toxicity]] relative to dose. Side effects associated with the use of yohimbine include anxiety, an increased urinary frequency, and increases in blood pressure at higher doses.<ref name="Biomedical">Reference Module in Biomedical Sciences | https://www.sciencedirect.com/science/article/pii/B9780128012383988627</ref> Higher doses (200 – 5,000 mg) result in stronger side effects and can be toxic to the brain. Extremely high doses (above 5,000 mg) can be lethal.<ref>Case study: two fatal case reports of acute yohimbine intoxication. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/23846025</ref>
 ===Dependence and abuse potential===
+Yohimbine may potentially be [[Addiction potential::mildly habit forming]] and the desire to use it may actually ''increase'' with use. However, in comparison to other more traditional [[stimulants]] such as [[amphetamine]] or [[methylphenidate]], it is not nearly as addictive or compulsive.
 ===Dangerous interactions===
 {{DangerousInteractions/Intro}}
+{{DangerousInteractions/Stimulants}}
+{{DangerousInteractions/MAOI|nt=dopamine}}
 ==Legal status==
 ==See also==