Tolazoline Dopamine

Solutions of drugs were prepared in 145 mM aqueous NaCl, from which a dose series was prepared. dl-Octopamine, dl-synephrine, dopamine, tolazoline, clonidine, yohimbine, cyproheptadine, gramine, chlorpromazine, promethazine, propranolol, metoclopramide, and 3-isobutyl-l-methylxanthine were obtained from Sigma Chemical Co. naphazoline from Aldrich Chemical Co. chlordimeform and phentolamine from Ciba Geigy mianserin from Research Biochemicals Inc. and lofexidine, XAMI, and tramazoline were gifts from Dr. R. Hollingworth, Purdue Univ. 

FIG. 17 Chemical structures of (a) epinephrine hydrochloride, (b) dopamine hydrochloride, (c) isoproterenol hydrochloride, (d) phenylephrine hydrochloride, (e) tolazoline hydrochloride, (f) oxyprenolol hydrochloride, (g) alprenolol hydrochloride, and (h) propranolol hydrochloride. 

Our agonist studies were designed to further document the effect of lower doses of OA on male sensitivity to pheromone (as shown in Figure 1), and to provide a pharmacological profile that could be compared with data from other published studies on OA receptors (12-14). The compounds included 1) the phenylethylamines synephrine and dopamine, 2) the formamidine chlordimeform, and 3) the substituted imidazolines naphazoline (2-[ 1-naphthylmethyl] imidazoline ), lofexidine (2-[ l-(2,6-dichlorophenoxy)ethyl]-2-imidazoline), XAMI (2,3-xylylaminomethyl-2-imidazoline), clonidine (2-(2,6-dichloro-anilino)-2-imidazoline), tolazoline (2-benzyl-2-imidazoline), and tramazoline (2-[5,6,7,8-tetrahydro-1-naphthyl]amino-2-imidazoline) ... 

The agonists were found to vary considerably in their potency, with peak response in chlordimeform and XAMI treated insects occurring at 1 pg/g vs 100 pg/g for OA (Figure 2). The dose-response curves also show that males treated with chlordimeform, XAMI, lofexidine naphazoline, and synephrine exhibited levels of response to 0.01 mg pheromone that were equal to those of OA-treated (100 pg/g) males, but that clonidine, tolazoline, and tramazoline were much less effective, and that dopamine was without effect on male sensitivity. 

Acute and eventually fatal hypotension occurred in a patient given dopamine and tolazoline. 

Not fully understood. Dopamine has both alpha (vasoconstrictor) and beta (vasodilator) activity. With the alpha effects on the systemic circulation competitively blocked by the tolazoline, its vasodilatory actions would predominate, resulting in paradoxical hypotension. 

Information is limited but this interaction would appear to be established. The authors of this report warn that an infusion of dopamine should not be considered for several hours after even a small single dose of tolazoline has been given. They point out that impaired renal function often accompanies severe respiratory failure, which may significantly prolong the effects of tolazoline. 

Carlon GC. Fatal association of tolazoline and dopamine. Chest( 9T9) 76, 336. 

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