Use of aminoglycosides to protect against excitotoxic neuron damage
US5677288A · kind A · utility
Assignee
Inventor
Key dates
| Filing date | Apr 15, 1994 |
| Grant date | Oct 14, 1997 |
| Priority date | — |
| Expiry date | Apr 15, 2014 |
Classification
- Technology area (CPC A)Human Necessities
- CPC primaryA61K31/7036
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
A method is disclosed for reducing excitotoxic damage to neurons, which can occur as a result of stroke, cardiac arrest, or other events or conditions. This method involves administering an aminoglycoside that suppresses the flow of calcium ions into neurons through N-type calcium channels. To be effective for such use, an aminoglycoside must suppress N-channel activity at a potency greater than streptomycin. Aminoglycosides which meet this criterion (which includes neomycin and Gentamicin) can suppress the depolarizing activation of neurons, which in turn controls the release of glutamate, a neurotransmitter that becomes an endogenous toxin under excitotoxic conditions. Numerous aminoglycosides were tested in in vitro screening tests using brain cell membrane fragments to evaluate N-channel blocking potency. Aminoglycosides with the highest N-channel blocking potency were then tested using (1) in vitro tests on hippocampal brain tissue, to evaluate recovery of neuronal activity after a period of oxygen deprivation; (2) in vivo tests to evaluate the control of induced seizures in intact adult mammals; and (3) in vivo tests to evaluate the reduction of brain damage due to surgically…
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.