Stable formulations of selective 5-hydroxytryptamine receptor antagonists for oral spray administration for absorption by the oral mucosa and related methods of preparation and administration are provided. A preferred embodiment includes ondansetron in a concentration of about 5.1 to about 5.2% w/w; propylene glycol in a concentration of about 60.1 to about 60.3% w/w; water in a concentration of about 5.3 to about 5.4% w/w; and ethanol in a concentration of about 27.1 to about 27.3% w/w. Additional preferred embodiments are preservative free and/or non-aqueous or primarily non-aqueous.