The availability of radiolabelled
ligands selective for various putative
neurotransmitter receptor sites and the development of quantitative autoradiography has led to a greater understanding of the neuronal pathway and receptor subtypes involved in the
vomiting reflex induced by various mechanisms both within the central nervous system and the periphery. Receptors for
acetylcholine,
dopamine,
histamine and
serotonin have been detected in a number of brain regions associated with the
vomiting reflex, and provide a rational basis for the
antiemetic action of drugs that inhibit receptor subtypes for these
neurotransmitters. The basis of the
antiemetic action of other drugs such as
dexamethasone and the
cannabinoids is still obscure. Some drugs act on more than 1 receptor subtype.
Metoclopramide may inhibit both
dopamine D2- and 5-HT3 receptors in producing its
antiemetic effect. Both
metoclopramide and
domperidone appear to have additional peripheral actions that contribute to their effectiveness. The
cannabinoids are effective in cytotoxic-induced
vomiting, perhaps acting via
endorphin receptors or by inhibiting
prostaglandin synthesis. The effectiveness of
5-HT3 receptor antagonists may depend on the block of both central and peripheral neuronal 5-HT3 receptors.
Vomiting constitutes a major disadvantage to the use of many drugs;
vomiting induced by
aminoglycoside antibiotics appears to be due to
ototoxicity and is relieved by
histamine H1-receptor antagonists. The protracted
vomiting associated with the use of some cytotoxics in
cancer chemotherapy may involve psychic components, the chemoreceptor trigger zone and peripheral sensory neurons. Both 5-HT3 and
dopamine D2-receptor antagonists exert some control, the former being more effective with cytotoxics of high emetogenic potential, such as
cisplatin.
Serotonin 5-HT3 receptor antagonists or high doses of
metoclopramide in combination with
anxiolytics and
steroids as well as greater attention to pharmacokinetic profiles of the drugs involved would appear to offer improved control. The use of
dopamine receptor antagonists in controlling
emesis induced by
dopamine agonists used in
Parkinson's disease poses theoretical problems which can be overcome by using drugs with selectivity for the chemoreceptor trigger zone, such as
domperidone or
metoclopramide. However, higher doses of these drugs may produce some impairment of therapeutic responses to the agonists.
Muscarinic and
nicotinic agonists currently under investigation in
Alzheimer's disease pose another therapeutic dilemma as
emesis is due to a central action of these compounds. Several sites may be involved including the chemoreceptor trigger zone and frontal lobes.
Opiates may act through
dopamine receptors or
mu-receptors on dopaminergic nerves, but serotonergic mechanisms may also be involved in the action of some
opiates.(ABSTRACT TRUNCATED AT 400 WORDS)