Phentolamine applications

Tolazoline is similar to phentolamine. Tolazoline has very limited clinical application in the treatment of pulmonary hypertension in newborn infants with respiratory distress syndrome. Its efficacy in this condition is doubtful, and the drug is rarely used. 

Neurotransmission resulting from NE release can be blocked by a variety of drugs that block adrenergic receptors. These may be a or p blockers depending on the situation. Application of NE mimics the effects of nerve stimulation and these effects can also be inhibited by the same drugs. Eor example, vasodilation produced by stimulation of sympathetic innervation of blood vessels can be blocked by a blocker of a adrenergic receptors such as phentolamine. 

Both phentolamine and tolazoline are potent but rather nonspecific a-antagonists. Both drugs stimulate gastrointestinal smooth muscle, an action blocked by atropine, which would indicate cholinergic activity, and they both stimulate gastric secretion, possibly through release of histamine. Because of these and other side effects, the clinical applications of tolazoline and phentolamine also are limited to treating the symptoms of pheochromocytoma. 

The original a-antagonists did not distinguish between ai- and a2 types and found only a few therapeutic applications, but they gave some help in frostbite and other, more long-term, cases of impaired circulation. Typical examples were the imidazolines such as phentolamine (12.48) and the chlorethylamines such as phenoxybenzamine (12.49). The latter became activated by self-quaternization (defined on p. 577) and caused irreversible alkylation of ar receptors. 

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