Modulation of receptor-mediated ion transport
AssigneeTrustees of Boston University
InventorDavid H. Farb
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Abstract
The subject application discloses methods for modulating NMDA-mediated ion transport, and inhibiting non-NMDA glutamate-induced ion transport, in neuronal cells. The methods involve contacting a neuronal cell with an effective amount of the neurosteroid pregnenolone sulfate, or pharmacologically effective derivatives thereof.
Claims34
A method for potentiating glutamate-induced NMDA receptor-mediated ion channel activity comprising contacting a neuronal cell with a pregnenolone sulfate solution at a concentration of about 1-500 micromolar.
A method for potentiating glutamate-induced NMDA receptor-mediated ion channel activity in a neuronal cell comprising contacting the neuronal cell with a solution comprising a derivative of pregnenolone sulfate in which the sulfate at position 3 of the steroid skeleton is replaced by an alkyl sulfate, the solution having a concentration of the derivative of pregnenolone sulfate of about 1-500 micromolar.
A method for potentiating glutamate-induced NMDA receptor-mediated ion channel activity in a neuronal cell comprising contacting the neuronal cell with a solution comprising a derivative of pregnenolone sulfate in which the sulfate at position 3 of the steroid skeleton is replaced by an alkyl sulfonate, the solution having a concentration of the derivative of pregnenolone sulfate of about 1-500 micromolar.
A method for potentiating glutamate-induced NMDA receptor-mediated ion channel activity in a neuronal cell comprising contacting the neuronal cell with a solution comprising a derivative of pregnenolone sulfate in which the sulfate at position 3 of the steroid skeleton is replaced by an alkyl acetate, the solution having a concentration of the derivative of pregnenolone sulfate of about 1-500 micromolar.
A method for potentiating glutamate-induced NMDA receptor-mediated ion channel activity in a neuronal cell comprising contacting the neuronal cell with a solution comprising a derivative of pregnenolone sulfate in which the steroid skeleton is modified to add the subsitituents selected from the group consisting of 5,6 dihydro, 5 hydroxy, 6 hydroxy, 5 methyl and 6 methyl, the solution having a concentration of the derivative of pregnenolone sulfate of about 1-500 micromolar.
A method for potentiating glutamate-induced NMDA receptor-mediated ion channel activity in a neuronal cell comprising contacting the neuronal cell with a solution comprising a derivative of pregnenolone sulfate having modifications selected from the group consisting of:
- a) substitution of the sulfate at position 3 of the steroid skeleton with a chemical group selected from the group consisting of alkyl sulfates, alkyl sulfonates and alkyl acetates;
- b) additions at position 5 of the steroid skeleton with a chemical group selected from the group consisting of dihydro, hydroxy and methyl;
- c) additions at position 6 of the steroid skeleton with a chemical group selected from the group consisting of dihydro, hydroxy and methyl;
- the solution having a concentration of the derivative of pregnenolone sulfate of about 1-500 micromolar.
A method for potentiating glutamate-induced NMDA receptor-mediated ion channel activity in a neuronal cell comprising contacting the neuronal cell with a solution comprising a pregnenolone sulfate derivative selected from the group consisting of dehydroepiandrosterone sulfate, tetrahydrodeoxycorticosterone sulfate, allotetrahydrodeoxycorticosterone sulfate, 3.alpha.-hydroxy-5.alpha.-pregnane-11,20-dione sulfate alfadolone sulfate and 3.alpha.-hydroxy-16-imino-5.beta.-17 aza-androstan-11-one sulfate, the solution having a concentration of the derivative of pregnenolone sulfate of about 1-500 micromolar.
A method for potentiating glutamate-induced NMDA receptor-mediated ion channel activity and inhibiting GABA or glycine-induced receptor-mediated ion channel activity comprising contacting a neuronal cell with a solution comprising pregnenolone sulfate, the solution having a concentration of pregnenolone sulfate of about 1-500 micromolar.
A method for potentiating glutamate-induced NMDA receptor-mediated ion channel activity and inhibiting GABA or glycine-induced receptor-mediated ion channel activity in a neuronal cell comprising contacting the neuronal cell with a solution comprising a derivative of pregnenolone sulfate in which the sulfate at position 3 of the steroid skeleton is replaced by an alkyl sulfate, the solution having a concentration of the derivative of pregnenolone sulfate of about 1-500 micromolar.
A method for potentiating glutamate-induced NMDA receptor-mediated ion channel activity and inhibiting GABA or glycine-induced receptor-mediated ion channel activity in a neuronal cell comprising contacting the neuronal cell with a solution comprising a derivative of pregnenolone sulfate in which the sulfate at position 3 of the steroid skeleton is replaced by an alkyl sulfonate, the solution having a concentration of the derivative of pregnenolone sulfate of about 1-500 micromolar.
A method for potentiating glutamate-induced NMDA receptor-mediated ion channel activity and inhibiting GABA or glycine-induced receptor-mediated ion channel activity in a neuronal cell comprising contacting the neuronal cell with a solution comprising a derivative of pregnenolone sulfate in which the sulfate at position 3 of the steroid skeleton is replaced by an alkyl acetate, the solution having a concentration of the derivative of pregnenolone sulfate of about 1-500 micromolar.
A method for potentiating glutamate-induced NMDA receptor-mediated ion channel activity and inhibiting GABA or glycine-induced receptor-mediated ion channel activity in a neuronal cell comprising contacting the neuronal cell with a solution comprising a derivative of pregnenolone sulfate in which the steroid skeleton is modified to add the substituents selected from the group consisting of 5,6 dihydro, 5 hydroxy, 6 hydroxy, 5 methyl and 6 methyl, the solution having a concentration of the derivative of pregnenolone sulfate of about 1-500 micromolar.
A method for potentiating glutamate-induced NMDA receptor-mediated ion channel activity and inhibiting GABA or glycine-induced receptor-mediated ion channel activity in a neuronal cell comprising contacting the neuronal cell with a solution comprising a derivative of pregnenolone sulfate having modifications selected from the group consisting of:
- a) substitution of the sulfate at position 3 of the steroid skeleton with a chemical group selected from the group consisting of alkyl sulfates, alkyl sulfonates and alkyl acetates;
- b) additions at position 5 of the steroid skeleton with a chemical group selected from the group consisting of dihydro, hydroxy and methyl;
- c) additions at position 6 of the steroid skeleton with a chemical group selected from the group consisting of dihydro, hydroxy and methyl;
- the solution having a concentration of the derivative of pregnenolone sulfate of about 1-500 micromolar.
A method for potentiating glutamate-induced NMDA receptor-mediated ion channel activity and inhibiting GABA or glycine-induced receptor-mediated ion channel activity in a neuronal cell comprising contacting the neuronal cell with a solution comprising a pregnenolone sulfate derivative selected from the group consisting of dehydroepiandrosterone sulfate, tetrahydrodeoxycorticosterone sulfate, allotetrahydrodeoxycorticosterone sulfate, 3.alpha.-hydroxy-5.alpha.-pregnane-11,20-dione sulfate alfadolone sulfate and 3.alpha.-hydroxy-16-imino-5.beta.-17 aza-androstan-11-one sulfate, the solution having a concentration of the derivative of pregnenolone sulfate of about 1-500 micromolar.
Dependencies are inferred from the claim text.