Tolazoline HCl belongs to the synthetic group of α-adrenergic blocking agents known as the imidazoline derivatives. It has been approved by the U.S. Food and Drug Administration (FDA) and indicated for the reversal of effects associated with xylazine in horses. It also will reverse the analgesic effects of α-agonists. Tolazoline antagonizes the effects of detomidine more completely, hastens recovery, and lasts longer than atipamezole.¹

Tolazoline is a vasodilator that has direct actions on blood vessels and also increases cardiac output. It can interact to some degree with histamine, adrenergic, and cholinergic receptors, but the mechanisms of its therapeutic effects are not clear. Tolazoline’s mechanism of action is by means of a direct effect on peripheral vascular smooth muscle and indirect effects produced, in part, by release of endogenous histamine. It has moderate α-adrenergic blocking activity and has histamine agonist activity. Tolazoline usually reduces pulmonary arterial pressure and vascular resistance. In humans, it is used in treatment of persistent pulmonary hypertension of the newborn.²

Effects of Tolazoline

In veterinary medicine, tolazoline is often used to reverse sedation and cardiovascular effects of xylazine in ruminants. It has also been used for reversing α-agonists in a variety of other species, but less safety and efficacy data is available. ³

Tolazoline is fast-acting (usually within 5 minutes of IV administration), but may not fully reverse effects on sedation or heart rate and rhythm. Its duration of action is relatively short, occasionally requiring repeat doses.² In horses that received detomidine (0.04 mg/kg sublingual) then tolazoline (4 mg/kg IV) 1 hour later, tolazoline’s effect on detomidine-induced changes in chin-to-ground distance were minimal; detomidine-induced changes in heart rate and rhythm only persisted for 15 to 20 minutes.⁴

After tolazoline doses of 4 mg/kg IV in horses, average heart rate decreased beginning 2 minutes postinjection, with heart rate nadir at 45 minutes. No apparent effect on chin-to-ground distance was noted. Packed cell volume significantly increased in all horses throughout the times sampled, with the maximal change at 15 minutes. Serum glucose concentrations increased significantly in all horses at the first time point measured through 1.5 hours postinjection.⁵

One 2013 study investigated the pharmacokinetics and pharmacodynamic effects of tolazoline when administered as a sole agent. Nine healthy adult horses were administered tolazoline (4 mg/kg IV) and blood samples were collected at time 0 (prior to drug administration) and at various times up to 72 h post drug administration. Plasma samples were analyzed using liquid chromatography–mass spectrometry and resulting data analyzed using compartmental analysis.⁶

The study found that systemic clearance, steady state volume of distribution and terminal elimination half-life were 0.820 ± 0.182 L/h/kg, 1.68 ± 0.379 L/kg and 2.69 ± 0.212 h, respectively. Tolazoline administration had no effect on chin to ground distance, but the heart rate decreased (relative to baseline) and the percentage of atrial–ventricular block increased in all horses within 2 min of administration. Packed cell volume and glucose concentrations were also increased throughout the sampling period.⁶

Cautions and Warnings

According to Plumb’s Veterinary Drugs, the following drug interactions have either been reported or are theoretical in humans or animals receiving tolazoline and may be of significance in veterinary patients:

Alcohol: Accumulation of acetaldehyde can occur if tolazoline and alcohol are given simultaneously.

Dopamine: Concurrent use may cause severe hypotension.

Epinephrine, Norepinephrine: If large doses of tolazoline are given with either norepinephrine or epinephrine, a paradoxical drop in blood pressure can occur followed by a precipitous increase in blood pressure.³

In horses given tolazoline alone (and no previous xylazine), doses 5 times the recommended dose resulted in GI hypermotility with resultant flatulence and defecation or attempt to defecate. Some horses exhibited mild colic and transient diarrhea. Intraventricular conduction may be slowed when horses are overdosed, with a prolongation of the QRS-complex noted.³

Tolazoline Dosages

Tolazoline dosages for equines per Plumb’s Veterinary Drugs are as follows (Note that Tolazoline is an ARCI Class 3 Drug):

Horses: Reversal of xylazine effects (labeled dose; FDA-approved): 4 mg/kg slow IV (4 mL/220 lb of body weight); administration rate should approximate 1 mL/second. (Package Insert; Tolazine®)

Horses: Reversal of xylazine effects (extra-label): 0.5 – 2 mg/kg IM (preferred) or slow IV; if administering IV, may wish to divide dose and give multiple smaller doses.

Horses: Reversal of low-dose α-agonist effects after dental procedures (extra-label): Following sedation with 1.1 – 2.2 mg/kg IM xylazine, reverse with tolazoline 0.04 mg/kg slow IV; may repeat 0.02 mg/kg slow IV 20-30 minutes later if needed.

Donkeys: Reversal of detomidine (extra-label): tolazoline 4 mg/kg IV given 15 minutes after detomidine 0.04 mg/kg IV reduced the degree and duration of sedation, ataxia, and analgesia.³

Where to buy Tolazoline

Tolazoline is available in the U.S. through several pharmaceutical manufacturers and through veterinary custom compounding companies.

Tolazoline (100 mg/ml) by NexGen is an excellent xylazine reversing agent and antagonist for intravenous use in horses, with minimal adverse effects typically presenting. Onset of arousal is generally apparent within 5 minutes of tolazoline administration, depending on the depth and duration of sedation.

FOR RX ONLY: A valid prescription from a licensed veterinarian is required for dispensing this medication.

¹Zeiler GE. A review of clinical approaches to antagonism of alpha(2)-adrenoreceptor agonists in the horse. Equine Veterinary Education. 2015;27(1):48-54.

²drugbank.com.

³Plumb’s Veterinary Drugs.

⁴Knych HK, Stanley SD. Effects of three antagonists on selected pharmacodynamic effects of sublingually administered detomidine in the horse. Vet Anaesth Analg. 2014;41(1):36-47.

⁵Casbeer C, Knych HK. Pharmacokinetics and pharmacodynamic effects of tolazoline following intravenous administration to horses. Vet J. 2013;196(3):504-509.

⁶Casbeera, H.C., Knychab, H.K. Pharmacokinetics and pharmacodynamic effects of tolazoline following intravenous administration to horses. The Veterinary Journal, Volume 196, Issue 3, June 2013, Pages 504-509.