Chemical compounds

A composition comprising a 5HT3 antagonist and a compound selected from

• 4-(2-Amino-acetyl)-2-(S)-(4-fluoro-2-methyl-phenyl)-piperazine-1-carboxylic acid (3,5-bis-trifluoromethyl-benzyl)-methyl-amide hydrochloride;
• 2-(S)-(4-Fluoro-2-methyl-phenyl)-piperazine-1-carboxylic acid [1-(R)-(3,5-bis-trifluoromethyl-phenyl)-ethyl]-methyl-amide methanesulphonate;
• and
• 2-(S)-(4-Fluoro-2-methyl-phenyl)-piperazine-1-carboxylic acid [1-(R)-(3,5-bis-trifluoromethyl-phenyl)-ethyl]-methyl-amide acetate.

A method for the treatment of acute emesis in a mammal comprising administering to said mammal an effective amount of a 5HT3 antagonist and a compound of formula (I):

• wherein
• *indicates a chiral carbon
• R is a halogen atom or a C1-4 alkyl group;
• R1 is hydrogen or a C1-4 alkyl group;
• R2 is hydrogen, a C1-4 alkyl, C2-6 alkenyl or a C3-7 cycloalkyl group;
• or R1 and R2 together with nitrogen and carbon atom to which they are attached respectively represent a 5-6 membered heterocyclic group;
• R3 is a trifluoromethyl, a C1-4 alkyl, a C1-4 alkoxy, a trifluoromethoxy or a halogen group;
• R4 is hydrogen, a (CH2)qR7 or a (CH2)rCO(CH2)pR7 group;
• R5 is hydrogen, a C1-4 alkyl or a COR6 group;
• R6 is hydrogen, hydroxy, amino, methylamino, dimethylamino a 5 membered heteroaryl group containing 1 to 3 heteroatoms selected from oxygen, sulphur and nitrogen or a 6 membered heteroaryl group containing 1 to 3 nitrogen atoms;
• R7 is hydrogen, hydroxy or NR8R9 wherein R8 and R9 represent independently hydrogen or C1-4 alkyl optionally substituted by hydroxy or by amino;
• R10 is hydrogen, a C1-4 alkyl group or R10 together with R2 represents a C3-7 cycloalkyl group;
• m is zero or an integer from 1 to 3;
• n is zero or an integer from 1 to 3;
• both p and r are independently zero or an integer from 1 to 4;
• q is an integer from 1 to 4;
• provided that, when R1 and R2 together with nitrogen and carbon atom to which they are attached respectively represent a 5 to 6 membered heterocyclic group,
• i) m is 1 or 2;
• ii) when m is 1, R is not fluorine and
• iii) when m is 2, the two substituents R are not both fluorine,
• or a pharmaceutically acceptable salt or solvate thereof.