| | In
order to improve the effectiveness of treatments and the quality
of patients' lives, it is important to control, or at least mitigate,
the damage wrought by nausea and vomiting. The search for effective
pharmacologic and behavioral methods of preventing or alleviating
these unpleasant and potentially dangerous treatment complications
has been an ongoing one since the serendipitous discovery that compazine
relieved emesis following the administration of nitrogen mustard.
Dopamine Receptor Antagonists
Early research showed
that antiemetics (typically phenothiazines and butyrophenones)
blocked dopamine receptors (Morrow,
1989; Wampler,
1983).
Metoclopramide, a substituted
benzamide, has been widely used as an antiemetic drug for more
than 27 years and was originally believed to act solely by blocking
dopamine receptors in the chemoreceptor trigger zone (Harrington
et al., 1983). However, its efficacy against the severe emetogenic
effects of chemotherapeutic agents, such as cisplatin, was very
limited.
As a consequence, high
dose metoclopramide (up to 10 mg/kg/day) was introduced and proved
to be more effective against cisplatin-induced emesis (Gralla
et al., 1981). This important development led to the conclusion
that some mechanism other than dopamine receptor blockade might
be producing the antiemetic effect by its action on 5-hydroxytryptamine
(5-HT3) receptors located on gut neurons
(Miner
et al., 1986).
|