Tolazoline (Imidaline)

Pharmacology of tolazoline

Tolazoline's complex pharmacologic effects likely represent the algebraic sum of primary, secondary, and possibly tertiary interactions with histamine and adrenergic receptors. Oxygenation improves initially in the majority of neonates with PPHN treated with tolazoline. Preliminary studies of tolazoline pharmacokinetics in the newborn indicate current doses are excessive and lead to accumulation, which may contribute to adverse effects, including cardiotoxicity.

Pulmonary vasodilator action of tolazoline

The pulmonary vasodilator action of tolazoline in newborn lambs was shown to be mediated via histamine receptors. Maximal changes in pulmonary vascular resistance, deltaPVR, were calculated as percents of the base line value, %deltaPVR. The mean %deltaPVR after tolazoline, 1 mg/kg, was -25 +/- 4% for eight lambs. Four lambs then received the histamine H1 receptor antagonist, diphenhydramine, and the mean %deltaPVR due to tolazoline was -12 +/- 4%. Four lambs received the H2 receptor antagonist, metiamide, and the mean %delta PVR due to tolazoline was -18 +/- 5%. After both H1 and H2 antagonists, the mean %deltaPVR due to tolazoline was +6 +/- 8%. Therefore, both histamine H1 and H2 receptors were involved in the vasodilator response to tolazoline.

Is nebulised tolazoline an effective treatment for persistent pulmonary hypertension of the newborn?

Tolazoline-induced apnea in mule deer (Odocoileus hemionus)

Eighteen mule deer (Odocoileus hemionus) and six Columbia black-tailed deer (Odocoileus hemionus columbianus) were held in pens and repeatedly anesthetized from April 2004 through June 2005 as part of an external parasite study. Deer were anesthetized using a combination of Telazol and xylazine hydrochloride (HCL) administered intramuscularly. Tolazoline HCL was slowly administered at 4 mg/kg intravenously to reverse the effects of xylazine with good results. For 17 of the 19 mule deer anesthesias in the fall of 2004, a mean dose of 7.3 mg/kg of intravenous tolazoline (range 6.1-8.4 mg/kg) was given by mistake. This paper describes clinical signs of apnea, muscle tensing, and fasciculations immediately following intravenous administration of tolazoline HCL in mule deer (O. hemionus) at 1.5-3 times the recommended dose. Mean dose for black-tailed deer during this time was 8.1 mg/kg (range 5.5-12.4 mg/kg) with no clinical signs as seen in the mule deer. Based on these findings, intravenous tolazoline use in mule deer is recommended at < or = 4 mg/kg.

Pharmacokinetics and pharmacodynamic effects of tolazoline following intravenous administration to horses

Tolazoline is an α2-adrenergic receptor antagonist, used in veterinary medicine to antagonize the central nervous system depressant and cardiovascular effects of α2 receptor agonists. The pharmacokinetics and pharmacodynamic effects of tolazoline when administered subsequent to detomidine in the horse were recently reported, although the reversal of the sedative and cardiovascular effects following detomidine may not be complete. The current study therefore investigated the pharmacokinetics and pharmacodynamic effects of tolazoline when administered as a sole agent. Nine healthy adult horses were administered tolazoline (4mg/kgIV) and blood samples were collected at time 0 (prior to drug administration) and at various times up to 72h post drug administration. Plasma samples were analyzed using liquid chromatography-mass spectrometry and resulting data analyzed using compartmental analysis. Systemic clearance, steady state volume of distribution and terminal elimination half-life were 0.820±0.182L/h/kg, 1.68±0.379L/kg and 2.69±0.212h, 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 2min of administration. Packed cell volume and glucose concentrations were also increased throughout the sampling period. While not commonly used as a sole agent, caution is indicated whenever tolazoline is administered since the effects may be unpredictable.