Description
Dolasetron is an antagonist of the serotonin (5-HT) receptor subtype 5-HT
3 (K
i = 20 nM). It is selective for 5-HT
3 receptors over 5-HT
1A, 5-HT
1B, 5-HT
2, dopamine D
2, α
1-, α
2-, β-adrenergic, M
1-5 muscarinic acetylcholine, and neurokinin-1 (NK
1) receptors (IC
50s = >10 μM for all). Dolasetron inhibits 5-HT-induced membrane currents in NG 108-15 cells (IC
50 = 3.8 nM). It increases the latency to emesis and reduces the number of vomiting and retching episodes induced by cisplatin in ferrets when administered at doses of 0.5 or 2 mg/kg. Formulations containing dolasetron have been used in the prevention of postoperative or chemotherapy-induced nausea.
Chemical Properties
White Solid
Uses
prevention and treatment of postoperative nausea and vomiting
Uses
Dolasetron is a bridged pseudopelletierine derivative; specific serotonin (5HT3) receptor antagonist.It is used as antiemetic.
Uses
Bridged pseudopelletierine derivative; specific serotonin (5HT3) receptor antagonist. Antiemetic.
Definition
ChEBI: LSM-5418 is an indolyl carboxylic acid.
brand name
Anzemet (Sanofi Aventis.
Synthesis
Ethyl cyclopentenecarboxylate (I), in the presence of a catalytic amount of osmium tetroxide, was oxidized to diol (II) with N-methylmorpholine-N-oxide. It was then split to dialdehyde (III) in the presence of sodium periodate and its aqueous solution was converted to bicyclization (IV) at pH 4 by Robinson-Schoepf reaction. (IV) was then reduced to alcohol (V) with sodium borohydride and reacted with dihydropyran to form tetrahydrofuran ether (VI) to protect the hydroxyl group formed. This is then converted to the tricyclic compound (VII), which is then acylated to give dolasetron by reacting with an acyl chloride (VIII) in the presence of silver tetrafluoroborate.
References
[1] PETER H. BOEIJINGA . Characterization of the novel 5-HT3 antagonists MDL 73147EF (dolasetron mesilate) and MDL 74156 in NG108-15 neuroblastoma × glioma cells[J]. European journal of pharmacology, 1992, 219 1: Pages 9-13. DOI:
10.1016/0014-2999(92)90573-m[2] ROBERT C. MILLER. Pharmacological properties of dolasetron, a potent and selective antagonist at 5-HT3 receptors[J]. Drug Development Research, 1993, 28 1: 87-93. DOI:
10.1002/ddr.430280111
