Yohimbine

Yohimbine is an alkaloid with stimulant and aphrodisiac effects found naturally in Pausinystalia yohimbe (Yohimbe). It is also found naturally in Rauwolfia serpentina (Indian Snakeroot), along with several other active alkaloids. Yohimbine has been used as both an over-the-counter dietary supplement in herbal extract form and prescription medicine in pure form for the treatment of sexual dysfunction. Yohimbine was explored as a remedy for type 2 diabetes in animal and human models carrying polymorphisms of the α2A-adrenergic receptor gene.

Sexual
The NIH states that yohimbine hydrochloride is the standardized form of yohimbine that is available as a prescription medicine in the United States, and has been shown in human studies to be effective in the treatment of male impotence.

Yohimbine Hydrochloride, USP&mdash;a standardized form of yohimbine&mdash;is a prescription medicine that has been used to treat erectile dysfunction. Controlled studies suggest that it is not always an effective treatment for impotence, and evidence of increased sex drive (libido) is anecdotal only.

Yohimbine blocks the pre- and post-synaptic alpha-2 adrenoceptors. Blockade of post-synaptic alpha-2 adrenoceptors leads to minor corpora cavernosa smooth muscle relaxation. In fact the majority of adrenoceptors in the corpora cavernosa are alpha-1. Blockade of pre-synaptic alpha-2 adrenoceptors leads to increased release of neurotransmitters in the Central Nervous System and in the corpora cavernosa penis such as nitric oxide, noradrenaline and dopamine. Whether Nitric Oxide released in the corpora cavernosa has a relaxing effect, noradrenaline has a much powerful constricting effect by stimulating the unblocked alpha-1 adrenoceptors. Concomitant use of an alpha-1 blocking agent will prevent constriction caused by the increased adrenergic stimulation.

Yohimbine has been shown to be effective in the reversal of sexual satiety and exhaustion in male rats. Yohimbine has also been shown to increase the volume of ejaculated semen in dogs, with the effect lasting at least five hours after administration. Yohimbine has been shown to be effective in the treatment of orgasmic dysfunction in men.

Fat loss
According to one study, oral yohimbine supplementation may actuate significant fat loss in athletes. Numerous bodybuilding supplement companies sell formulations of yohimbine for transdermal delivery to effect a local reduction of adipose tissue, although the experimental evidence for its efficiency is limited.

Other uses
Yohimbine has also been used for the treatment of sexual side effects caused by some antidepressants (SSRIs), female hyposexual disorder, as a blood pressure boosting agent in autonomic failure, xerostomia, and as a probe for noradrenergic activity.

The addition of yohimbine to fluoxetine or venlafaxine has also been found to potentiate the antidepressant action of both of these agents.

Yohimbine has been used to facilitate recall of traumatic memories in the treatment of post traumatic stress disorder (PTSD). Use of yohimbine outside therapeutic settings may not be appropriate for persons suffering from PTSD. In pharmacology, yohimbine is used as a probe for α2-adrenoceptor. In veterinary medicine, yohimbine is used to reverse anesthesia from the drug xylazine in small and large animals.

Pharmacology
Yohimbine has high affinity for the α2-adrenergic receptor, moderate affinity for the α1-adrenergic, 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1F, 5-HT2B, and D2 receptors, and weak affinity for the 5-HT1E, 5-HT2A, 5-HT5A, 5-HT7, and D3 receptors. It behaves as an antagonist at α1-adrenergic, α2-adrenergic, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, and D2, and as a partial agonist at 5-HT1A. Its intrinsic activities at the other sites listed are unclear/unknown, but it is probably mostly antagonistic at them.

Production
Yohimbine is the principal alkaloid of the bark of the West African evergreen Pausinystalia yohimbe (formerly Corynanthe yohimbe), family Rubiaceae (Madder family). There are 31 other yohimbane alkaloids found in Yohimbe. In Africa, yohimbe has traditionally been used as an aphrodisiac. However, it is very important to note that while the terms yohimbine, yohimbine hydrochloride, and yohimbe bark extract are related, they are not interchangeable.

The main active chemical present in yohimbe bark is yohimbine HCl (indole alkaloid), found in the bark of the Pausinystalia yohimbe tree.

However, the levels of yohimbine that are present in yohimbe bark extract are variable and often very low. Therefore, although yohimbe bark has been used traditionally to reduce male erectile dysfunction, there is not enough scientific evidence to form a definitive conclusion in this area.

The tree is currently threatened with extinction in its native habitat due to international demand. Its conservation is difficult because the bioactivity of the tree has led many Western governments to declare it a proscribed species.

Adverse effects
Yohimbine has significant side effects, such as anxiety reactions. According to the Mayo Clinic, yohimbine can be dangerous if used in excessive amounts.

Higher doses of oral yohimbine may create numerous side effects, such as rapid heart rate, high blood pressure, overstimulation, insomnia and/or sleeplessness. Some effects in rare cases were panic attacks, hallucinations, headaches, dizziness, and skin flushing.

More serious adverse effects may include seizures and renal failure. Yohimbine should not be consumed by anyone with liver, kidney, heart disease, or a psychological disorder.

The therapeutic index of yohimbine is quite low; the range between an effective dose and a dangerous dose is very narrow. This may also lead to precipitation of panic disorder type reactions.

Yohimbine in combination with modafinil is frequently associated with nausea, dangerous acute rapid heart beat, and acute increased blood pressure. Yohimbine exhibits some degree of MAOI activity while modafinil has been shown to increase levels of various monamines, and therefore could result in severe risk of dangerous side effects.