Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...
Reexamination Certificate
2001-10-31
2004-12-07
Fay, Zohreh (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Nitrogen containing other than solely as a nitrogen in an...
Reexamination Certificate
active
06828351
ABSTRACT:
BACKGROUND OF THE INVENTION
The term “memory” subsumes many different processes and requires the function of many different brain areas. Overall, human memory provides declarative recall, e.g., for facts and events accessible to conscious recollection, and non-declarative recall, e.g., procedural memory of skills and operations not stored regarding time and place. Research in recent years has provided information necessary to understand many of the various components of memory and has identified associated brain regions. A newly acquired experience initially is susceptible to various forms of disruption. With time, however, the new experience becomes resistant to disruption. This observation has been interpreted to indicate that a labile, working, short-term memory is consolidated into a more stable, long-term memory.
Behavioral research has found that the human mind consolidates memory at certain key time intervals. The initial phase of memory consolidation occurs in the first few minutes after an exposure to a new idea or learning experience. The next phase occurs over a longer period of time, such as during sleep. If a learning experience has on-going meaning to us, the next week or so serves as a further period of memory consolidation. In effect, in this phase, the memory moves from short-term to long-term storage.
Moreover, various mechanisms have been proposed to account for the formation of long-term memory. A wide range of observations suggest an evolutionarily conserved molecular mechanism involved with the formation of long-term memory. These include increased release of synaptic transmitter, increased number of synaptic receptors, decreased K
D
of receptors, synthesis of new memory factors either in the presynaptic or postsynaptic clement, sprouting of new synaptic connections, increase of the active area in the presynaptic membrane and many others. Synaptic plasticity, the change in the strength of neuronal connections in the brain, is thought to underlie long-term memory storage.
“Memory consolidation”, or long-term memory is also believed to play a crucial role in a variety of neurological and mental disorders, including mental retardation, Alzheimer's disease and depression. Indeed, loss or impairment of long-term memory is a significant feature of such diseases, and no effective therapy for that effect has emerged. Short-term, or “working” memory, is generally not significantly impaired in such patients.
Accordingly, methods and compositions that enhance long-term memory function and/or performance, or prophylactically (e.g., as a neuroprotective treatment) prevent or slow degradation of long-term memory function and/or performance would be desirable. Similarly, methods and compositions for restoring long-term memory function and/or performance are needed.
SUMMARY OF THE INVENTION
The present invention relates to the discovery that the amphetamine class of compounds (collectively referred to herein as “amphetamine compounds”) can be used to enhance, prevent and/or restore long-term memory function and performance, e.g., to improve long-term memory (LTM) in animal subjects. More particularly, the invention relates to the discovery that a particular enantiomer of amphetamine compounds is effective for such therapeutic use.
One aspect of the invention features a pharmaceutical kit comprising one or more amphetamine compound(s) in an amount sufficient to enhance long-term memory in a patient, a pharmaceutically acceptable carrier, and instructions (written and/or pictorial) describing the use of the formulation for enhancing memory.
Another aspect of the invention features a pharmaceutical preparation comprising one or more amphetamine compounds provided as a single oral dosage formulation in an amount sufficient to enhance long-term memory in a patient but resulting in a concentration in the patient lower than its EC50 as a CNS stimulant.
Another aspect of the invention features a pharmaceutical preparation comprising one or more amphetamine compounds provided in the form of a transdermal patch and formulated for sustained release of the amphetamine(s) in order to administer an amount sufficient to enhance long-term memory in a patient but resulting in a concentration in the patient lower than its EC50 as a CNS stimulant.
In preferred embodiments the pharmaceutical kits and preparations of this invention comprise at least one of the amphetamine compounds represented by Formula I, or a pharmaceutically acceptable salt, solvate, metabolite or pro-drug thereof:
wherein, as valence and stability permit,
R
1
, independently for each occurrence, represents hydrogen or substituted or unsubstituted lower alkyl, lower alkenyl, lower alkynyl, aratkyl, aryl, heteroaralkyl, heteroaryl, cycloalkyl, or cycloalkylalkyl;
R
2
represents hydrogen or substituted or unsubstituted lower alkyl, lower alkenyl, lower alkynyl, aralkyl, aryl, heteroaralkyl, heteroaryl, cycloalkyl, or cycloalkylalkyl;
R
3
represents hydrogen or substituted or unsubstituted lower alkyl, lower alkenyl, lower alkynyl, aralkyl, aryl, heteroaralkyl, heteroaryl, cycloalkyl, or cycloalkylalkyl;
R
4
represents from 1 to 3 substituents on the ring to which it is attached, selected from the group consisting of hydrogen, halogen, hydroxy, alkoxy, amino, alkylamino, sulflydryl, alkylthio, cyano, nitro, ester, ketone, formyl, amido, acylamino, acyloxy, lower alkyl, lower alkenyl, sulfonate ester, amidino, sulfonyl, sulfoxido, sulfamoyl, and sulfonamido.
In certain embodiments, R
3
represents hydrogen, while in other embodiments, R
3
represents lower alkyl, such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, t-butyl, etc., hydroxy, amino, or carbonyl.
In certain embodiments, R
4
represents hydrogen, while in other embodiments, R
4
represents from 1 to 3 substituents on the ring to which it is attached selected from halogen, hydroxy, amino, sulfhydryl, cyano, nitro, lower alkyl, and sulfate.
In certain embodiments, R
4
represents hydrogen and at least one of R1, R
2
, and R
3
represents hydrogen. In certain embodiments, R
4
represents hydrogen and at least two of R
1
, R
2
, and R
3
represents hydrogen. In certain embodiments, R
4
represents hydrogen and at least three of R
1
, R
2
, and R
3
represent hydrogen. In certain embodiments, R
4
represents hydrogen and all four of R
1
, R
2
, and R
3
represent hydrogen.
In certain embodiments, one R
1
represents hydrogen, one R
1
represents lower alkyl, such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, t-butyl, etc., R
2
represents lower alkyl, such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, t-butyl, etc., R
3
and R
4
represent hydrogen.
In certain preferred embodiments, one occurrence of R
1
represents hydrogen, the second occurrence of R
1
represents hydrogen, or lower alkyl; R
2
represents hydrogen or lower alkyl, R
3
represents hydrogen or lower alkyl, and R
4
represents hydrogen or from 1 to 3 substituents on the ring to which it is attached, selected from halogen, trifluoromethyl, hydroxy, amino, cyano, nitro, and lower alkyl.
In certain preferred embodiments, R
4
represents hydrogen and at least one of R
1
, R
2
, and R
3
represents hydrogen.
In certain preferred embodiments, R
4
represents hydrogen and at least two of R
1
, R
2
, and R
3
represent hydrogen.
In certain preferred embodiments, both occurrences of R
1
represent independently hydrogen, R
2
represents methyl, R
3
represents hydrogen and R
4
represents hydrogen.
In certain preferred embodiments, one occurrence of R
1
represents hydrogen, the second occurrence of R
1
represents methyl, R
2
represents methyl, R
3
represents hydrogen and R
4
represents hydrogen.
In most preferred embodiments, R
1
, independently and for each occurrence, represents hydrogen, R2 represents methyl, and R
3
and R
4
independently and for each occurrence represent hydrogen.
In other preferred embodiments the pharmaceutical kits and preparations of this invention comprise at least one of the amphetamine compounds as a pharmaceutically acceptable salt represe
Epstein Mel
Wiig Kjesten A.
Fay Zohreh
Hamilton Brook Smith & Reynolds P.C.
Kwon Brian-Yong S.
Sention, Inc.
LandOfFree
Methods and compositions for regulating memory consolidation does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Methods and compositions for regulating memory consolidation, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods and compositions for regulating memory consolidation will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3324768