Reversal of drug-induced neuromuscular block using novel molecular containers
Provided are methods for reversing the effects of agents used for muscular immobilization and/or loss of consciousness and/or loss of pain perception. The method comprises administering a composition comprising acyclic CB[n]-type compounds to an individual in need of reversal of the effects of neuromuscular blocking agents and/or anesthetic agents such that the effects of the agent(s) are partially fully reversed.
1. A method for reversing drug-induced neuromuscular block and/or anesthesia in an individual comprising administering to an individual in need of reversal of neuromuscular block and/or anesthesia a composition comprising a compound having the following structure:
or a salt, a partial salt, a hydrate, or a stereoisomer thereof,
wherein each R is independently hydrogen, C 1 to C 20 alkyl group, C 3 to C 20 carbocyclic group, C 1 to C 20 heterocyclic group, carboxylic acid group, ester group, amide group, hydroxy, or ether group;
wherein, optionally, adjacent R groups form a C 3 to C 20 carbocyclic ring or heterocyclic ring;
wherein each
is independently a C 5 to C 20 carbocyclic ring system or C 2 to C 20 heterocyclic ring system, wherein the ring system comprises one or more rings;
wherein at least one ring system has at least one solubilizing group selected from sulfonic acid group, sulfonate salt group, phosphonic acid group, phosphonate salt group, and polyethylene glycol group;
wherein, optionally, the ring system has a targeting group;
wherein n is 1 to 5.
2. The method of claim 1 , wherein each
is independently a C 5 to C 20 carbocyclic ring system having one of the following structures:
wherein at each occurrence of
R 1 to R 16 is independently hydrogen, C 1 to C 20 alkyl group, halo group, hydroxyl group, nitro group, carboxylic acid group, ester group, amide group, ether group, C 3 to C 20 carbocyclic group, or C 1 to C 20 heterocyclic group,
provided that at least one of R 1 to R 16 in the compound has the following structure:
wherein LG is a linking group and X is the solubilizing group; and
wherein optionally one or more adjacent R 1 to R 16 groups are connected forming a carbocyclic ring or heterocyclic ring.
3. The method of claim 2 , wherein
has the following structure:
wherein each i is 1 to 20.
4. The method of claim 2 , wherein at least one of the R 1 to R 16 groups in the structure has the following structure:
and wherein LG is a linking group and wherein TG is the targeting group.
5. The method of claim 2 , wherein the
groups are the same.
6. The method of claim 3 , wherein the compound has one of the following structures:
wherein Z is PEG group having a molecular weight of 200 to 10,000.
7. The method of claim 1 , wherein the compound has one of the following structures:
wherein A + is H + , Na + , K + , Ca 2+ , Mg 2+ , Zn 2+ , H 4 N + , Et 3 NH + , Me 4 N + , (HOCH 2 CH 2 ) 3 NH + , or a cationic form of ethylenediamine, piperazine, and trishydroxymethyl aminomethane (TRIS).
8. The method of claim 1 , wherein the individual is in need of reversal of drug-induced neuromuscular block.
9. The method of claim 1 , wherein the individual is in need of reversal of anesthesia.
10. The method of claim 1 , wherein the individual is in need of reversal of drug-induced neuromuscular block and anesthesia.
11. The method of claim 1 , wherein the individual in need is a human.
12. The method of claim 1 , wherein the individual in need is a non-human mammal.