NOVEL METABOLITES OF VANOXERINE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME AND METHODS OF TERMINATING ACUTE EPISODES OF CARDIAC ARRHYTHMIA, RESTORING NORMAL SINUS RHYTHM, PREVENTING RECURRENCE OF CARDIAC ARRHYTHMIA AND MAINTAINING NORMAL SINUS RHYTHM IN MAMMALS
Disclosed embodiments are related to pharmaceutical compositions comprising novel piperazine compounds and methods of administration of the same to a patient for termination acute episodes of cardiac arrhythmias, maintaining normal sinus rhythm, restoring normal sinus rhythm, and preventing recurrence of cardiac arrhythmia.
1 . A piperazine compound having the following structure:
wherein R1, R2, R3, R4/R4′, R5/R5′, R6/R6′, R7/R7′, or R8, are either a hydrogen atom or a hydroxide and further provided that not all of R1, R2, R3, R4/R4′, R5/R5′, R6/R6′, R7/R7′, or R8 are a hydrogen atom, and that only one of R1, R2, R3, R4/R4′, R5/R5′, R6/R6′, R7/R7′, or R8 is a hydroxide.
2 . The piperazine compound of claim 1 wherein one of R4 or R4′ is a hydroxide.
3 . The piperazine compound of claim 1 wherein one of R5 or R5′ is a hydroxide.
4 . The piperazine compound of claim 1 wherein one of R6 or 64′ is a hydroxide.
5 . The piperazine compound of claim 1 wherein one of R7 or R7′ is a hydroxide.
6 . The piperazine compound of claim 1 wherein R8 is a hydroxide.
7 . A pharmaceutical composition comprising a piperazine compound having the following structure:
wherein R1, R2, R3, R4/R4′, R5/R5′, R6/R6′, R7/R7′, or R8, are either a hydrogen atom or a hydroxide and further provided that not all of R1, R2, R3, R4/R4′, R5/R5′, R6/R6′, R7/R7′, or R8 are a hydrogen atom, and that only one of R1, R2, R3, R4/R4′, R5/R5′, R6/R6′, R7/R7′, or R8 is a hydroxide, in admixture with a pharmaceutically acceptable carrier suitable for administration to a mammal.
8 . The piperazine compound of claim 1 wherein one of R4 or R4′ is a hydroxide.
9 . The piperazine compound of claim 1 wherein one of R5 or R5′ is a hydroxide.
10 . The piperazine compound of claim 1 wherein one of R6 or 64′ is a hydroxide.
11 . The piperazine compound of claim 1 wherein one of R7 or 74′ is a hydroxide.
12 . The piperazine compound of claim 1 wherein R8 is a hydroxide.
13 . A method of administration a pharmaceutical compound comprising the piperazine compound having the following structure:
wherein R1, R2, R3, R4/R4′, R5/R5′, R6/R6′, R7/R7′, or R8, are either a hydrogen atom or a hydroxide and further provided that not all of R1, R2, R3, R4/R4′, R5/R5′, R6/R6′, R7/R7′, or R8 are a hydrogen atom, and that only one of R1, R2, R3, R4/R4′, R5/R5′, R6/R6′, R7/R7′, or R8 is a hydroxide, comprising the method of administering an effective amount of one or more of the novel piperazine compounds to a mammal for the treatment of cardiac arrhythmia.
14 . The method of claim 13 wherein the cardiac arrhythmia is atrial fibrillation or ventricular fibrillation.
15 . The method of claim 13 wherein the treatment of cardiac arrhythmia is restoring normal sinus rhythm in a mammal.
16 . The method of claim 13 wherein the treatment of cardiac arrhythmia is an acute episode of cardiac arrhythmia.
17 . The method of claim 13 wherein the effective amount of the one or more novel piperazine compounds results in a plasma concentration of said one or more piperazine compounds of between about 20 and about 200 ng/ml at one hour post administration.
18 . The method of claim 13 wherein the effective amount of the one or more novel piperazine compounds results in a plasma concentration of said one or more piperazine compounds of between about 20 and about 150 ng/ml at one hour post administration.
19 . The method of claim 13 wherein the effective amount of the one or more novel piperazine compounds results in a plasma concentration of said one or more piperazine compounds of between about 60 and about 125 ng/ml at one hour post administration.
20 . The method of claim 13 wherein the effective amount of the one or more novel piperazine compounds results in a plasma concentration of said one or more piperazine compounds of between about 20 and about 200 ng/ml at between 0 and four hours post administration.