Cisplatin-like chemotherapeutics cause vomiting via release of multiple 
neurotransmitters (dopamine, serotonin (5-HT), or substance P (SP)) from the 
gastrointestinal enterochromaffin cells and/or the brainstem via a calcium 
dependent process. Diverse channels in the plasma membrane allow extracellular 
Ca(2+) entry into cells for the transmitter release process. Agonists of 5-HT3 
receptors increase calcium influx through both 5-HT3 receptors and L-type Ca(2+) 
channels. We envisaged that L-type calcium agonists such as FPL 64176 should 
cause vomiting and corresponding antagonists such as nifedipine would behave as 
broad-spectrum antiemetics. Administration of FPL 64176 did cause vomiting in 
the least shrew in a dose-dependent fashion. Nifedipine and the 5-HT3 receptor 
antagonist palonosetron, potently suppressed FPL 64176-induced vomiting, while a 
combination of ineffective doses of these antagonists was more efficacious. 
Subsequently, we investigated the broad-spectrum antiemetic potential of 
nifedipine against diverse emetogens including agonists of serotonergic 5-HT3- 
(e.g. 5-HT or 2-Me-5-HT), SP tachykinin NK1- (GR73632), dopamine D2- 
(apomorphine or quinpirole), and cholinergic M1- (McN-A-343) receptors, as well 
as the non-specific emetogen, cisplatin. Nifedipine by itself suppressed 
vomiting in a potent and dose-dependent manner caused by the above emetogens 
except cisplatin. Moreover, low doses of nifedipine potentiated the antiemetic 
efficacy of non-effective or semi-effective doses of palonosetron against 
vomiting caused by either 2-Me-5-HT or cisplatin. Thus, our findings demonstrate 
that activation of L-type calcium channels causes vomiting, whereas blockade of 
these ion channels by nifedipine-like antagonists not only provides 
broad-spectrum antiemetic activity but can also potentiate the antiemetic 
efficacy of well-established antiemetics such as palonosetron. L-type calcium 
channel antagonists should also provide antiemetic activity against drug-induced 
vomiting as well as other emetogens including bacterial and viral proteins.