Yohimbine

Br J Pharmacol. 1990 Sep;101(1):115-20.

Phentolamine and yohimbine inhibit ATP-sensitive K+ channels in mouse pancreatic beta-cells.[Pubmed: 2282453 ]

1. The effects of phentolamine and Yohimbine on adenosine 5'-triphosphate (ATP)-sensitive K+ channels were studied in normal mouse beta-cells.
METHODS AND RESULTS:
2. In the presence of 3 mM glucose, many ATP-sensitive K+ channels are open in the beta-cell membrane. Under these conditions, phentolamine inhibited 86Rb efflux from the islets. This inhibition was faster with 100 than with 20 microM phentolamine but its steady-state magnitude was similar with both concentrations. Yohimbine (20-100 microM) also inhibited the efflux rate but was not as potent as phentolamine. 3. In the presence of 6 mM glucose, most ATP-sensitive K+ channels are closed in the beta-cell membrane. Their opening by 100 microM diazoxide caused a marked acceleration of 86Rb efflux from the islets. This acceleration was almost entirely prevented by 20 microM phentolamine. It was barely affected by 20 microM Yohimbine and reduced by 50% by 100 microM Yohimbine. 4. ATP-sensitive K+ currents were studied in single beta-cells by the whole cell patch-clamp technique. Phentolamine (20-100 microM) caused a progressive but almost complete and irreversible inhibition of the current. The effects of Yohimbine were faster but smaller; the inhibition was still incomplete with 100 microM Yohimbine. 5. The increase in ATP-sensitive K+ current produced by 100 microM diazoxide was prevented by 100 microM phentolamine but only partially attenuated by 100 microM Yohimbine.
CONCLUSIONS:
6. It is concluded that phentolamine inhibits ATP-sensitive K+ channels in pancreatic beta-cells. This novel effect of phentolamine resembles that of hypoglycaemic sulphonylureas. It may account for previously unexplained effects of the drug. These observations also call for reinterpretation of many studies in which phentolamine was used as an allegedly specific blocker of alpha-adrenoceptors.

Biol Psychiatry. 2014 Jun 1;75(11):840-6.

Yohimbine enhancement of exposure therapy for social anxiety disorder: a randomized controlled trial.[Pubmed: 24237691]

Preclinical and clinical trials suggest that Yohimbine may augment extinction learning without significant side effects. However, previous clinical trials have only examined adults with specific phobias. Yohimbine has not yet been investigated in the augmentation of exposure therapy for other anxiety disorders.
METHODS AND RESULTS:
Adults (n = 40) with a DSM-IV diagnosis of social anxiety disorder were randomized to placebo or Yohimbine HCl (10.8 mg) 1 hour before each of four exposure sessions. Outcome measures were collected at baseline, each treatment session, posttreatment, and 1-month follow-up. Yohimbine was well tolerated. Yohimbine augmentation, relative to placebo augmentation, resulted in faster improvement and better outcomes on self-report measures of social anxiety disorder severity (Liebowitz Social Anxiety Scale, d = .53) and depressed mood severity (Beck Depression Inventory, d = .37) but not on the clinician-rated measures (Clinical Global Impressions-Severity Scale, d = .09; Clinical Global Impressions-Improvement Scale, d = .25). Between-group differences on the Liebowitz Social Anxiety Scale were moderated by the level of fear reported at the end of an exposure exercise (end fear), such that the advantage of Yohimbine over placebo was only evident among patients who reported low end fear.
CONCLUSIONS:
The results provide moderate support for Yohimbine as a therapeutic augmentation strategy for exposure therapy in social anxiety disorder, one that may be especially effective when coupled with successful exposure experiences. Beneficial effects for Yohimbine were readily evident for self-report measures but not for clinician-rated outcomes of social anxiety severity and improvement.

Psychopharmacology (Berl). 2007 Dec;195(3):345-55.

The CRF1 receptor antagonist antalarmin attenuates yohimbine-induced increases in operant alcohol self-administration and reinstatement of alcohol seeking in rats.[Pubmed: 17705061 ]

Yohimbine is an alpha-2 adrenoreceptor antagonist that provokes stress- and anxiety-like responses in both humans and laboratory animals. In rats, Yohimbine increases operant alcohol self-administration and reinstates alcohol seeking. In this study, we assess whether these effects of Yohimbine are attenuated by systemic injections of the corticotrotropin-releasing factor 1 (CRF1) receptor antagonist antalarmin.
METHODS AND RESULTS:
In Exp. 1, we trained rats to lever press for alcohol solutions (12% w/v, 1 h/day) over several weeks; during training, the response requirement was increased from a fixed-ratio-1 (FR-1) to a fixed-ratio-3 (FR-3) reinforcement schedule. We then tested the effect of antalarmin (10 or 20 mg/kg) on Yohimbine (1.25 mg/kg)-induced increases in operant alcohol self-administration (FR-3 reinforcement schedule). Subsequently, we assessed the effect of antalarmin on Yohimbine-induced increases in plasma corticosterone levels in the previously self-administering rats. In Exp. 2, we trained the rats to self-administer alcohol as in Exp. 1, and after extinction of the alcohol-reinforced lever responding over 13 days, we tested antalarmin's effect on Yohimbine-induced reinstatement of alcohol seeking. Yohimbine increased operant alcohol self-administration and reinstated alcohol seeking after extinction. These effects of Yohimbine were attenuated by antalarmin. Antalarmin injections in the absence of Yohimbine had no effect on either operant alcohol self-administration or extinction responding. Antalarmin had no effect on Yohimbine-induced corticosterone release in alcohol-experienced rats.
CONCLUSIONS:
These results suggest that extrahypothalamic CRF1 receptors are involved in the effect of Yohimbine on operant alcohol self-administration and on relapse to alcohol seeking and support the notion that CRF1 receptor antagonists should be considered in alcohol addiction treatment.

Can J Vet Res. 2014 Oct;78(4):304-15.

Antagonistic effects of atipamezole, yohimbine, and prazosin on xylazine-induced diuresis in clinically normal cats.[Pubmed: 25356000]

This study aimed to investigate and compare the antagonistic effects of atipamezole, Yohimbine, and prazosin on xylazine-induced diuresis in clinically normal cats.
METHODS AND RESULTS:
Five cats were repeatedly used in each of the 9 groups. One group was not medicated. Cats in the other groups received 2 mg/kg BW xylazine intramuscularly, and saline (as the control); 160 μg/kg BW prazosin; or 40, 160, or 480 μg/kg BW atipamezole or Yohimbine intravenously 0.5 h later. Urine and blood samples were collected 10 times over 8 h. Urine volume, pH, and specific gravity; plasma arginine vasopressin (AVP) concentration; and creatinine, osmolality, and electrolyte values in both urine and plasma were measured. Both atipamezole and Yohimbine antagonized xylazine-induced diuresis, but prazosin did not. The antidiuretic effect of atipamezole was more potent than that of Yohimbine but not dose-dependent, in contrast to the effect of Yohimbine at the tested doses. Both atipamezole and Yohimbine reversed xylazine-induced decreases in both urine specific gravity and osmolality, and the increase in free water clearance. Glomerular filtration rate, osmolar clearance, and plasma electrolyte concentrations were not significantly altered. Antidiuresis of either atipamezole or Yohimbine was not related to the area under the curve for AVP concentration, although the highest dose of both atipamezole and Yohimbine increased plasma AVP concentration initially and temporarily, suggesting that this may in part influence antidiuretic effects of both agents. The diuretic effect of xylazine in cats may be mediated by α2-adrenoceptors but not α1-adrenoceptors.
CONCLUSIONS:
Atipamezole and Yohimbine can be used as antagonistic agents against xylazine-induced diuresis in clinically normal cats.

J AOAC Int. 2015 Mar-Apr;98(2):330-5.

Characterization and quantitation of yohimbine and its analogs in botanicals and dietary supplements using LC/QTOF-MS and LC/QQQ-MS for determination of the presence of bark extract and yohimbine adulteration.[Pubmed: 25905738]

The compound Yohimbine HCl has been restricted in Australia and categorized as a scheduled prescription drug in other parts of the world, including the United States where it is monographed as a drug in the U. S. Pharmacopeia. However, the bark of the yohimbe plant and its extract is considered a botanical that can be used as a dietary supplement in some parts of the world. For these reasons, methods to characterize the indole alkaloids of the bark and quantify Yohimbine and its analogs are presented using accurate mass LC/quadrupole time-of-flight (QTOF)-MS and triple quadrupole LC/MS, respectively.
METHODS AND RESULTS:
Samples were extracted with a QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) method to characterize and quantify the indole alkaloids. With the LC/QTOF-MS in auto MS/MS mode the indole alkaloids were identified, and the isomeric response of each could be used to determine whether the actual bark or extract was in samples of dietary supplements and not adulteration with Yohimbine HCl. Analogs were identified and include yohimbic acid, methyl Yohimbine, and hydroxyl Yohimbine. Many isomers of each were also detected, but identified only by the number of chromatographic peaks. Quantification of Yohimbine and ajmalicine spiked extracts showed recoveries of 99 to 103% with RSD of 3.6% or lower and LODs of less than 100 ppt. Calibration of the two standards gave r(2) = 0.9999 in a range from 0.1 to 100 ppb.
CONCLUSIONS:
Dietary supplements quantified for these two compounds showed a range from not detected to 3x the amounts found in the bark.