Cancer serotonin receptor antagonists

Nausea that accompanies the administration of cancer chemotherapy agents was resistant to drug intervention until the introduction of the serotonin receptor antagonist odansetron (see Chapter 13). The benzimidazolone-based compound itasetron (57-6) has much the same activity as its tricylcic predecessor. Condensation of 2-nitrophenyl-isocyanate (57-1) with the bridged bycyclic diamine (57-2) leads to the addition... 

Dr David Graham from the FDA, speaking to the US senate in 2004, controversially raised concerns (refuted by the respective Pharmaceutical Companies) over the safety of the retinoid, isotretinoin (used in the treatment of cancer), the statin, rosuvastatin (used to lower cholesterol), a long-acting p2-receptor antagonist, salmeterol (used in asthma therapy), and a selective serotonin reuptake inhibitor, paroxetine (used as an antidepressant) (21). 

Odansetron is an antagonist of the serotonin receptor 5-HT3. Its main use is in combating the nausea and vomiting which frequently accompanies treatment with anti-cancer chemotherapy. In one short-term, 4-week placebo-controlled trial involving 26 patients with severe BN, odansetron 24 mg daily halved the frequency of binging and vomiting (Faris et al. 2000). Two other small clinical trials support the use of odansetron in BN (Fung and Ferrill 2001). 

Ondansetron, a serotonin (5-HT3)-receptor antagonist (0.15 mg/kg IV with the first dose taken infused every 15 minutes before the start of chemotherapy), is used in the prevention of nansea and vomiting associated with initial and repeat conrses of emetogenic cancer chemotherapy, including high-dose cisplatin (see Figure 73). 

HTj (a serotonin receptor—see following chapter) antagonists ondansetron (commonly used in cancer chemotherapy), granisetron... 

Serotoninergic 5-HT3 receptors (cationic) transduce the effects of serotonin (5-hydroxy tryptamine, 5-HT), altogether with others 5-HT receptors which are GPCR. Selective 5-HT3 antagonists, like ondansetron and analogs, are antiemetics used during cancer therapy. 

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