BrainMeta'   Connectomics'  

Welcome Guest ( Log In | Register )

 
Reply to this topicStart new topic
> PRL-8-53 --- 3-(2-benzylmethylamino ethyl) benzoic acid methyl ester, "PRL-8-53 gives the average person a memory span of about 21 to 22 digits." - Durk Pearson, 'High Frontiers'
Ricardas Tarvydas
post Dec 25, 2008, 02:57 PM
Post #1


Newbie
*

Group: Basic Member
Posts: 7
Joined: Dec 16, 2008
Member No.: 31800




Phi Delta Kappan - December 1979 - Vol 61 - pages 264-265

Learning and Memory Improvement Through Chemistry: Dream or Reality in the Offing?
by Nikolaus R. Hansl and Adele B. Hansl
The 'smart pill' may, at last, be only a testing period away. It is PRL-8-53.

The news story read: "A team of Creighton University health science researchs is working with an experimental drug that could be just what the `absent-minded professor' has been needing for years."

The story was based on a news release by the Federation of American Societies for Experimental Biology. Good credentials for sure, but what are the facts supporting such statements? How is it possible for a drug, a single chemical conpound, to have a positive effect on the function of the brain, which is such an an enormously complex system? What has been the clinical experience so far, and what can we learn from laboratory findings?

The last clinical report, a paper by Nikolaus Hansl, Adele B. Hansl, and Beverley T. Mead given in Portland at the meeting of the American Society for Pharmacology and Experimental Therapeutics, reported that retention of verbal information (nonsense syllables) improved by 80% for subjects who had taken PRL-8-53 when compared to the same subjects' learning when on a placebo. This confirmed an earlier report on the sme drug, published in Experientia, reporting increased acquisition and retention in another group of volunteers.

Intellectual function comprises many factors, and as we are learning now, individual distinctive functional characteristics such as perception, short-term memory, long-term memory, correlation, retrieval, to name but a few, appear to be chemically controlled by their specific agonist-receptor systems within the neuronal latticework. In other words, it seems to be possible to augment or suppress one or more of these specific capabilities by chemical means, i.e., by amplifying or inhibiting chemical signals in control of the respective neuronal pathways.

We do have evidence regarding the identity of some chemical correlates. Recall from "long-term memory," retrieval of information that has been accumulated over a period of time, seems mediated by acetylcholine and the cholinergic system. Inhibition of this system in the experimental animal by drugs such as atropine or scopolamine greatly impairs recall capacity or performance dependent on it. By the same token, a boost of the cholinergic system by a drug such as physostigmine improve recall-dependent performance.

Actually, this latter drug has been used with some success in humans in Alzheimer Disease, which involves severe pre-senile memory loss. The problems with physostigmine are toxicity and practicality. Aside from the fact that the positive effects with this drug were observed within a very narrow dose range (less having no effect at all and a slightly higher dose causing considerable side effects), physostigmine, in order to achieve the desired effect, had to be given by an intravenous drip infusion.

In contrast, the drug reported by us, PRL-8-53, has been shown to enhance the respose to acetylcholine, the response being quantititatively similar over a considerable dose range, excluding the likelihood of accidental overdosing. The compound may be taken orally, and it is active over a period of several hours. The drug is not a stimulant, andin the experimental animal toxicity appears only after it is given a dose more than one thousand times as large as the projected human dose. In summary, we now have a potentially useful drug that will boost a specific chemical system in the brain, the cholinergic system, and thereby improve our ability to recall, to retrieve information from a pre-existing information pool. Other important chemical effects have been attributed to this drug, but space does not permit us to cover the more detailed information here.

Long-term memory, the type of information referred to above, is laid down in the brain in the form of a chemical code. In order to effect a synthesis of the informational molecules, we now believe it to be necessary to effect a transition from an earlier code, whic referred to as short-term memory. This transition, which is a chemical process, appears to depend on the mediation of another chemical system using noradrenaline as the chemical messenger. PRL-8-53 has been shown to augment responses to noradrenaline in the animal model both peripherally and centrally. Therefore, it seems reasonable to assume that a similar function may be present in humans. Translated into behavioral effects, it implies that this drug is also capable of facilitating the conversion of short-term to long-term memory, causing an increased storage of informational code. We now have a data base supporting the notion that we can modulate chemical systems in the brain, systems that are involved in or are mediating intellectual function. It further appears that we are able to affect these systems in such a way as to improve performance.



In one series of tests the subjects were asked to memorize simple words by listening to a tape recording. In another test slides with lists of words were projected for a given time, and again subjects were asked to memorize these lists. These two different tests enabled us to see whether learning was improved regardless of which one of the two most commonly used patheways of information input was used. We found that acquisition and subsequent retention improved following drug intake to a similar extent in both experiments.

Having establised that acquisition and retention of verbal information could be positively affected by the drug, we considered it important to look at nonverbal areas. We used the Benton test, exposing geometric patterns for brief periods to the subjects, then asking them to draw the figures as they remembered them. Again we found statistically significant improvement when subjects were on the drug.

To explore still another area, we deisgned a test to determine how number manipulation might be affected. Our subjects rand through a somewhat complex countdown maneuver. Subjects had to subtract seven from a given starting number, then add one, subtract seven and add tow, subtract seven and add three then subtract seven then add one, and so on until they reached the goal number. This was a timed test and again we found improvement, i.e., shorter test times when subjects had taken the drug. In a final test we asked our subjects to complete words from dot-letter-dot-letter combinations (e.g., U.R.). Words could be extended on either side. The only requirements: The words must be in English (even slang), and the spelling for the letters replacing the dots must be correct (e.g., cUrRent). Here we tried to see how long the drug would affect recall from an existing information pool. The information retrieved in this test is also subject to a certain amount of intellectual manipulation. In effect, the test might be considered a verbal fluency test. Again we found statistically significant improvement when the subjects had taken the drug prior to testing.

Having established the spectrum of effectiveness in students, or at least a part of it, we wanted to learn how an older population subgroup would respond. A number of colleagues volunteered and took the verbal learning and retention test. This group as age 30 or older. As might be expected, rote memory did not come as easily to this group as it did to the younger students. The average retention after 24 hours when on placebo was just under three words out of a possible 12. The average retention after one week was two words. However, the same subjects, when learning subsequent to drug administration, retained an average of 5.85 words after 24 hours and 5.25 words after one week. Again the increases were statistically significant. The improvement expressed in percent of placebo performance was 108% for the 24 hour test and 152% for the one-week recal.

The above tests all concerned the effects of PRL-8-53 on acquisition and memory. At this time we have only limited experience with drug effects on higher integrating functions of the brain, such as association and correlation. Moreover, our experience in this area is limted to animal responses. We designed experiments specifically aimed at measuring correlation, or what we conceive as possibly a rudimentary capacity of conceptual understanding. There was significantly improved performance after administration of the drug, but we do not know whether we shall find similar positive responses from humans. Even conservative extrapolations from experimental animals to humans are risky.

ANother area that has not been discussed is one of much concern: learning disabilities. With so many different causes underlying disabilities, no generalizations can be made. Where there is anatomical damage, the prognosis for benefits from PRL-8-53 would not be good. In the case of chemical aberrations as the only cause of a learning disability, any possible drug effect would depend on the nature of the aberration. Drug effects must be investigated for each type of disability; only experimentation will bring answers.

In summary, it appears that a number of important parameters of intellectual function are amenable to drug action. Improvement does ot seem limited to the young; the older group actually experienced a greater relative improvement in the test. However, just as the extent of improvement varied from one group to another, so did the response from one individual to the next. This is to be expected. The drug seems to augment some weak link in the chain of events related to intellectual function. This link is weaker for some than for others. The individual net effect is not predictable and will vary. We certainly are not dealing with a compound that would act as a great equalizer. Although some people with quite different base levels of performance might end up in close proximity, others will still be apart in performance. The important thing is that, regardless of initial performane level, improvment can still be achieved.

Finally, let us emphasize that we are dealing with an experimental compound; much investigation will be neccessary and many questions must be answered. So, while there is hope for the "absent minded professor" as well as for the student, both must wait until all regulatory requirements are met -- and we hope -- this or a related compound becomes available for use in the improvement of learning.

NIKOLAUS R. HANSL is a neuropharmacologist at Creighton University, Omaha, Nebr. He holds the Ph.D. from the University of Vienna. ADELE B. HANSL is his wife and research associate. The research reported here is based on a clinical report made by the Hansls and Beverley T. Mead at the August 1979 meeting of the American Society for Pharmacology and Experimental Therapeutics.





Is anyone aware of this substance? I would be grateful for updated information as I have not been able to find any. All medical research documents are almost 20 years old. It looks like that research has stopped with no particular reason.

And from what I have read this substance works well and is non toxic. Correct me if I am wrong.
User is offlineProfile CardPM
Go to the top of the page
+Quote Post
LifeMirage
post Dec 25, 2008, 03:31 PM
Post #2


Demi-God
*****

Group: Global Mod
Posts: 974
Joined: Apr 13, 2005
From: Netherlands
Member No.: 4349



QUOTE(Ricardas Tarvydas @ Dec 25, 2008, 04:57 PM) *

Phi Delta Kappan - December 1979 - Vol 61 - pages 264-265

Learning and Memory Improvement Through Chemistry: Dream or Reality in the Offing?
by Nikolaus R. Hansl and Adele B. Hansl
The 'smart pill' may, at last, be only a testing period away. It is PRL-8-53.

The news story read: "A team of Creighton University health science researchs is working with an experimental drug that could be just what the `absent-minded professor' has been needing for years."

The story was based on a news release by the Federation of American Societies for Experimental Biology. Good credentials for sure, but what are the facts supporting such statements? How is it possible for a drug, a single chemical conpound, to have a positive effect on the function of the brain, which is such an an enormously complex system? What has been the clinical experience so far, and what can we learn from laboratory findings?

The last clinical report, a paper by Nikolaus Hansl, Adele B. Hansl, and Beverley T. Mead given in Portland at the meeting of the American Society for Pharmacology and Experimental Therapeutics, reported that retention of verbal information (nonsense syllables) improved by 80% for subjects who had taken PRL-8-53 when compared to the same subjects' learning when on a placebo. This confirmed an earlier report on the sme drug, published in Experientia, reporting increased acquisition and retention in another group of volunteers.

Intellectual function comprises many factors, and as we are learning now, individual distinctive functional characteristics such as perception, short-term memory, long-term memory, correlation, retrieval, to name but a few, appear to be chemically controlled by their specific agonist-receptor systems within the neuronal latticework. In other words, it seems to be possible to augment or suppress one or more of these specific capabilities by chemical means, i.e., by amplifying or inhibiting chemical signals in control of the respective neuronal pathways.

We do have evidence regarding the identity of some chemical correlates. Recall from "long-term memory," retrieval of information that has been accumulated over a period of time, seems mediated by acetylcholine and the cholinergic system. Inhibition of this system in the experimental animal by drugs such as atropine or scopolamine greatly impairs recall capacity or performance dependent on it. By the same token, a boost of the cholinergic system by a drug such as physostigmine improve recall-dependent performance.

Actually, this latter drug has been used with some success in humans in Alzheimer Disease, which involves severe pre-senile memory loss. The problems with physostigmine are toxicity and practicality. Aside from the fact that the positive effects with this drug were observed within a very narrow dose range (less having no effect at all and a slightly higher dose causing considerable side effects), physostigmine, in order to achieve the desired effect, had to be given by an intravenous drip infusion.

In contrast, the drug reported by us, PRL-8-53, has been shown to enhance the respose to acetylcholine, the response being quantititatively similar over a considerable dose range, excluding the likelihood of accidental overdosing. The compound may be taken orally, and it is active over a period of several hours. The drug is not a stimulant, andin the experimental animal toxicity appears only after it is given a dose more than one thousand times as large as the projected human dose. In summary, we now have a potentially useful drug that will boost a specific chemical system in the brain, the cholinergic system, and thereby improve our ability to recall, to retrieve information from a pre-existing information pool. Other important chemical effects have been attributed to this drug, but space does not permit us to cover the more detailed information here.

Long-term memory, the type of information referred to above, is laid down in the brain in the form of a chemical code. In order to effect a synthesis of the informational molecules, we now believe it to be necessary to effect a transition from an earlier code, whic referred to as short-term memory. This transition, which is a chemical process, appears to depend on the mediation of another chemical system using noradrenaline as the chemical messenger. PRL-8-53 has been shown to augment responses to noradrenaline in the animal model both peripherally and centrally. Therefore, it seems reasonable to assume that a similar function may be present in humans. Translated into behavioral effects, it implies that this drug is also capable of facilitating the conversion of short-term to long-term memory, causing an increased storage of informational code. We now have a data base supporting the notion that we can modulate chemical systems in the brain, systems that are involved in or are mediating intellectual function. It further appears that we are able to affect these systems in such a way as to improve performance.



In one series of tests the subjects were asked to memorize simple words by listening to a tape recording. In another test slides with lists of words were projected for a given time, and again subjects were asked to memorize these lists. These two different tests enabled us to see whether learning was improved regardless of which one of the two most commonly used patheways of information input was used. We found that acquisition and subsequent retention improved following drug intake to a similar extent in both experiments.

Having establised that acquisition and retention of verbal information could be positively affected by the drug, we considered it important to look at nonverbal areas. We used the Benton test, exposing geometric patterns for brief periods to the subjects, then asking them to draw the figures as they remembered them. Again we found statistically significant improvement when subjects were on the drug.

To explore still another area, we deisgned a test to determine how number manipulation might be affected. Our subjects rand through a somewhat complex countdown maneuver. Subjects had to subtract seven from a given starting number, then add one, subtract seven and add tow, subtract seven and add three then subtract seven then add one, and so on until they reached the goal number. This was a timed test and again we found improvement, i.e., shorter test times when subjects had taken the drug. In a final test we asked our subjects to complete words from dot-letter-dot-letter combinations (e.g., U.R.). Words could be extended on either side. The only requirements: The words must be in English (even slang), and the spelling for the letters replacing the dots must be correct (e.g., cUrRent). Here we tried to see how long the drug would affect recall from an existing information pool. The information retrieved in this test is also subject to a certain amount of intellectual manipulation. In effect, the test might be considered a verbal fluency test. Again we found statistically significant improvement when the subjects had taken the drug prior to testing.

Having established the spectrum of effectiveness in students, or at least a part of it, we wanted to learn how an older population subgroup would respond. A number of colleagues volunteered and took the verbal learning and retention test. This group as age 30 or older. As might be expected, rote memory did not come as easily to this group as it did to the younger students. The average retention after 24 hours when on placebo was just under three words out of a possible 12. The average retention after one week was two words. However, the same subjects, when learning subsequent to drug administration, retained an average of 5.85 words after 24 hours and 5.25 words after one week. Again the increases were statistically significant. The improvement expressed in percent of placebo performance was 108% for the 24 hour test and 152% for the one-week recal.

The above tests all concerned the effects of PRL-8-53 on acquisition and memory. At this time we have only limited experience with drug effects on higher integrating functions of the brain, such as association and correlation. Moreover, our experience in this area is limted to animal responses. We designed experiments specifically aimed at measuring correlation, or what we conceive as possibly a rudimentary capacity of conceptual understanding. There was significantly improved performance after administration of the drug, but we do not know whether we shall find similar positive responses from humans. Even conservative extrapolations from experimental animals to humans are risky.

ANother area that has not been discussed is one of much concern: learning disabilities. With so many different causes underlying disabilities, no generalizations can be made. Where there is anatomical damage, the prognosis for benefits from PRL-8-53 would not be good. In the case of chemical aberrations as the only cause of a learning disability, any possible drug effect would depend on the nature of the aberration. Drug effects must be investigated for each type of disability; only experimentation will bring answers.

In summary, it appears that a number of important parameters of intellectual function are amenable to drug action. Improvement does ot seem limited to the young; the older group actually experienced a greater relative improvement in the test. However, just as the extent of improvement varied from one group to another, so did the response from one individual to the next. This is to be expected. The drug seems to augment some weak link in the chain of events related to intellectual function. This link is weaker for some than for others. The individual net effect is not predictable and will vary. We certainly are not dealing with a compound that would act as a great equalizer. Although some people with quite different base levels of performance might end up in close proximity, others will still be apart in performance. The important thing is that, regardless of initial performane level, improvment can still be achieved.

Finally, let us emphasize that we are dealing with an experimental compound; much investigation will be neccessary and many questions must be answered. So, while there is hope for the "absent minded professor" as well as for the student, both must wait until all regulatory requirements are met -- and we hope -- this or a related compound becomes available for use in the improvement of learning.

NIKOLAUS R. HANSL is a neuropharmacologist at Creighton University, Omaha, Nebr. He holds the Ph.D. from the University of Vienna. ADELE B. HANSL is his wife and research associate. The research reported here is based on a clinical report made by the Hansls and Beverley T. Mead at the August 1979 meeting of the American Society for Pharmacology and Experimental Therapeutics.





Is anyone aware of this substance? I would be grateful for updated information as I have not been able to find any. All medical research documents are almost 20 years old. It looks like that research has stopped with no particular reason.

And from what I have read this substance works well and is non toxic. Correct me if I am wrong.


Unless it was effective for any medical condition and had pharmaceutical companies funding it the research usually stops. Only 2 studies show up in PubMed's database. I'll see if I can acquire the full articles for further review.

QUOTE
Psychopharmacology (Berl). 1978 Apr 11;56(3):249-53.
PRL-8-53: enhanced learning and subsequent retention in humans as a result of low oral doses of new psychotropic agent.

Hansl NR, Mead BT.

The effect of 3-(2-benzylmethylaminoethyl) benzoic acid methyl ester hydrochloride (PRL-8-53) on learning and on retention of verbal information in human subjects was investigated. Using the serial anticipation method under double-blind conditions it was found that PRL-8-53 causes slight improvement of acquisition. Retinetion of verbal information was found improved to a statistically significant degree (most P values better than 0.01, some better than 0.001). No significant changes were found for either visual reaction time or motor control after drug when compared with placebo values.

Experientia. 1974 Mar 15;30(3):271-2.
A novel spasmolytic and CNS active agent: 3-(2-benzylmethylamino ethyl) benzoic acid methyl ester hydrochloride. Hansl NR

User is offlineProfile CardPM
Go to the top of the page
+Quote Post
LifeMirage
post Dec 25, 2008, 03:40 PM
Post #3


Demi-God
*****

Group: Global Mod
Posts: 974
Joined: Apr 13, 2005
From: Netherlands
Member No.: 4349



http://www.freepatentsonline.com/3870715.html


User is offlineProfile CardPM
Go to the top of the page
+Quote Post
LifeMirage
post Dec 25, 2008, 03:43 PM
Post #4


Demi-God
*****

Group: Global Mod
Posts: 974
Joined: Apr 13, 2005
From: Netherlands
Member No.: 4349



Full article for the first study.


http://www.springerlink.com/content/k57653...22/fulltext.pdf
User is offlineProfile CardPM
Go to the top of the page
+Quote Post
Ricardas Tarvydas
post Dec 25, 2008, 04:34 PM
Post #5


Newbie
*

Group: Basic Member
Posts: 7
Joined: Dec 16, 2008
Member No.: 31800



Thanks a lot, take a look: uk dot youtube dot com/watch?v=ElCDG9j1fow
User is offlineProfile CardPM
Go to the top of the page
+Quote Post
LifeMirage
post Dec 25, 2008, 04:46 PM
Post #6


Demi-God
*****

Group: Global Mod
Posts: 974
Joined: Apr 13, 2005
From: Netherlands
Member No.: 4349



QUOTE(Ricardas Tarvydas @ Dec 25, 2008, 06:34 PM) *
Thanks a lot, take a look: uk dot youtube dot com/watch?v=ElCDG9j1fow


http://uk.youtube.com/watch?v=ElCDG9j1fow

Creative.
User is offlineProfile CardPM
Go to the top of the page
+Quote Post
Pike
post Dec 25, 2008, 05:18 PM
Post #7


Newbie
*

Group: Basic Member
Posts: 11
Joined: Dec 14, 2008
Member No.: 31798



This looks terribly interesting. I wonder if the original company funding the research would be interested in sending out test samples.
User is offlineProfile CardPM
Go to the top of the page
+Quote Post
LifeMirage
post Dec 25, 2008, 05:33 PM
Post #8


Demi-God
*****

Group: Global Mod
Posts: 974
Joined: Apr 13, 2005
From: Netherlands
Member No.: 4349



QUOTE(Pike @ Dec 25, 2008, 07:18 PM) *
This looks terribly interesting. I wonder if the original company funding the research would be interested in sending out test samples.


Considering the legal issues with giving out an unapproved drug and it being over 20 years I would doubt it.
It would be easier to have a chemist with the proper equipment make some. However I would not encourage this.
User is offlineProfile CardPM
Go to the top of the page
+Quote Post
Ricardas Tarvydas
post Dec 25, 2008, 05:50 PM
Post #9


Newbie
*

Group: Basic Member
Posts: 7
Joined: Dec 16, 2008
Member No.: 31800



QUOTE
Unless it was effective for any medical condition and had pharmaceutical companies funding it the research usually stops.


Considering that this substance is non toxic it could have been effective enough to become a very popular supplement, doping for students or the ones with poor memory... Perhaps someone did not want it to become a sell able product. You can find many products with unproven effectiveness and they are very popular.
User is offlineProfile CardPM
Go to the top of the page
+Quote Post
LifeMirage
post Dec 25, 2008, 06:35 PM
Post #10


Demi-God
*****

Group: Global Mod
Posts: 974
Joined: Apr 13, 2005
From: Netherlands
Member No.: 4349



QUOTE(Ricardas Tarvydas @ Dec 25, 2008, 07:50 PM) *
QUOTE
Unless it was effective for any medical condition and had pharmaceutical companies funding it the research usually stops.


Considering that this substance is non toxic it could have been effective enough to become a very popular supplement, doping for students or the ones with poor memory... Perhaps someone did not want it to become a sell able product. You can find many products with unproven effectiveness and they are very popular.


And yet after nearly 30 years nothing. I don't expect this to be available. There are natural compounds already available for memory otc.
User is offlineProfile CardPM
Go to the top of the page
+Quote Post
Underman
post Mar 05, 2010, 12:04 PM
Post #11


Newbie
*

Group: Basic Member
Posts: 4
Joined: Mar 05, 2010
Member No.: 32645



QUOTE(LifeMirage @ Dec 25, 2008, 06:35 PM) *

QUOTE(Ricardas Tarvydas @ Dec 25, 2008, 07:50 PM) *
QUOTE
Unless it was effective for any medical condition and had pharmaceutical companies funding it the research usually stops.


Considering that this substance is non toxic it could have been effective enough to become a very popular supplement, doping for students or the ones with poor memory... Perhaps someone did not want it to become a sell able product. You can find many products with unproven effectiveness and they are very popular.


And yet after nearly 30 years nothing. I don't expect this to be available. There are natural compounds already available for memory otc.


really? Like what? Racetams don't count, they're prescription in every country and are considered an unaproved drug here as well. As far as I know they're the only med that safely and consistently enhances memory past choline supplements and a few herbs, mushrooms. If there was something that could permanently enhance working, short, and long term memory it would be a bigger medication than statins, ssri's, and antipsychotics put together.
User is offlineProfile CardPM
Go to the top of the page
+Quote Post
changshageorge78
post Oct 21, 2010, 11:23 PM
Post #12


Newbie
*

Group: Basic Member
Posts: 1
Joined: Oct 21, 2010
Member No.: 33167



You're right that research on this particular compound is about 20 years old or longer...PRL 8-53, was listed and discussed in the journal of "Drugs of the Future." It's chemical structure was given in that publication. This publication is hard to find....you'll need to go to a medical interlibrary loan provider to locate this specific article. Also you might find it interesting that PRL-8-53, demonstrated enhanced performance in visual processing. Incidentally, PRL 8-53 was replaced by a more potent compound known as PRL 8-147, it's likely that you will not find any research on this preparation either...Dr. Hansl, at the time was also developing a similar type of compound which was discribed in the journal called the "Pharmacologist," A brief description of this compound was mentioned in a public press magazine known as "Longevity"....this magazine, as far as I know, is not in publication any longer. If you want to look into Dr. Hansl's earlier work, check out the Nebraska Academy of Sciences for further citations. I hope you find this information useful.






QUOTE(Ricardas Tarvydas @ Dec 25, 2008, 02:57 PM) *


Phi Delta Kappan - December 1979 - Vol 61 - pages 264-265

Learning and Memory Improvement Through Chemistry: Dream or Reality in the Offing?
by Nikolaus R. Hansl and Adele B. Hansl
The 'smart pill' may, at last, be only a testing period away. It is PRL-8-53.

The news story read: "A team of Creighton University health science researchs is working with an experimental drug that could be just what the `absent-minded professor' has been needing for years."

The story was based on a news release by the Federation of American Societies for Experimental Biology. Good credentials for sure, but what are the facts supporting such statements? How is it possible for a drug, a single chemical conpound, to have a positive effect on the function of the brain, which is such an an enormously complex system? What has been the clinical experience so far, and what can we learn from laboratory findings?

The last clinical report, a paper by Nikolaus Hansl, Adele B. Hansl, and Beverley T. Mead given in Portland at the meeting of the American Society for Pharmacology and Experimental Therapeutics, reported that retention of verbal information (nonsense syllables) improved by 80% for subjects who had taken PRL-8-53 when compared to the same subjects' learning when on a placebo. This confirmed an earlier report on the sme drug, published in Experientia, reporting increased acquisition and retention in another group of volunteers.

Intellectual function comprises many factors, and as we are learning now, individual distinctive functional characteristics such as perception, short-term memory, long-term memory, correlation, retrieval, to name but a few, appear to be chemically controlled by their specific agonist-receptor systems within the neuronal latticework. In other words, it seems to be possible to augment or suppress one or more of these specific capabilities by chemical means, i.e., by amplifying or inhibiting chemical signals in control of the respective neuronal pathways.

We do have evidence regarding the identity of some chemical correlates. Recall from "long-term memory," retrieval of information that has been accumulated over a period of time, seems mediated by acetylcholine and the cholinergic system. Inhibition of this system in the experimental animal by drugs such as atropine or scopolamine greatly impairs recall capacity or performance dependent on it. By the same token, a boost of the cholinergic system by a drug such as physostigmine improve recall-dependent performance.

Actually, this latter drug has been used with some success in humans in Alzheimer Disease, which involves severe pre-senile memory loss. The problems with physostigmine are toxicity and practicality. Aside from the fact that the positive effects with this drug were observed within a very narrow dose range (less having no effect at all and a slightly higher dose causing considerable side effects), physostigmine, in order to achieve the desired effect, had to be given by an intravenous drip infusion.

In contrast, the drug reported by us, PRL-8-53, has been shown to enhance the respose to acetylcholine, the response being quantititatively similar over a considerable dose range, excluding the likelihood of accidental overdosing. The compound may be taken orally, and it is active over a period of several hours. The drug is not a stimulant, andin the experimental animal toxicity appears only after it is given a dose more than one thousand times as large as the projected human dose. In summary, we now have a potentially useful drug that will boost a specific chemical system in the brain, the cholinergic system, and thereby improve our ability to recall, to retrieve information from a pre-existing information pool. Other important chemical effects have been attributed to this drug, but space does not permit us to cover the more detailed information here.

Long-term memory, the type of information referred to above, is laid down in the brain in the form of a chemical code. In order to effect a synthesis of the informational molecules, we now believe it to be necessary to effect a transition from an earlier code, whic referred to as short-term memory. This transition, which is a chemical process, appears to depend on the mediation of another chemical system using noradrenaline as the chemical messenger. PRL-8-53 has been shown to augment responses to noradrenaline in the animal model both peripherally and centrally. Therefore, it seems reasonable to assume that a similar function may be present in humans. Translated into behavioral effects, it implies that this drug is also capable of facilitating the conversion of short-term to long-term memory, causing an increased storage of informational code. We now have a data base supporting the notion that we can modulate chemical systems in the brain, systems that are involved in or are mediating intellectual function. It further appears that we are able to affect these systems in such a way as to improve performance.



In one series of tests the subjects were asked to memorize simple words by listening to a tape recording. In another test slides with lists of words were projected for a given time, and again subjects were asked to memorize these lists. These two different tests enabled us to see whether learning was improved regardless of which one of the two most commonly used patheways of information input was used. We found that acquisition and subsequent retention improved following drug intake to a similar extent in both experiments.

Having establised that acquisition and retention of verbal information could be positively affected by the drug, we considered it important to look at nonverbal areas. We used the Benton test, exposing geometric patterns for brief periods to the subjects, then asking them to draw the figures as they remembered them. Again we found statistically significant improvement when subjects were on the drug.

To explore still another area, we deisgned a test to determine how number manipulation might be affected. Our subjects rand through a somewhat complex countdown maneuver. Subjects had to subtract seven from a given starting number, then add one, subtract seven and add tow, subtract seven and add three then subtract seven then add one, and so on until they reached the goal number. This was a timed test and again we found improvement, i.e., shorter test times when subjects had taken the drug. In a final test we asked our subjects to complete words from dot-letter-dot-letter combinations (e.g., U.R.). Words could be extended on either side. The only requirements: The words must be in English (even slang), and the spelling for the letters replacing the dots must be correct (e.g., cUrRent). Here we tried to see how long the drug would affect recall from an existing information pool. The information retrieved in this test is also subject to a certain amount of intellectual manipulation. In effect, the test might be considered a verbal fluency test. Again we found statistically significant improvement when the subjects had taken the drug prior to testing.

Having established the spectrum of effectiveness in students, or at least a part of it, we wanted to learn how an older population subgroup would respond. A number of colleagues volunteered and took the verbal learning and retention test. This group as age 30 or older. As might be expected, rote memory did not come as easily to this group as it did to the younger students. The average retention after 24 hours when on placebo was just under three words out of a possible 12. The average retention after one week was two words. However, the same subjects, when learning subsequent to drug administration, retained an average of 5.85 words after 24 hours and 5.25 words after one week. Again the increases were statistically significant. The improvement expressed in percent of placebo performance was 108% for the 24 hour test and 152% for the one-week recal.

The above tests all concerned the effects of PRL-8-53 on acquisition and memory. At this time we have only limited experience with drug effects on higher integrating functions of the brain, such as association and correlation. Moreover, our experience in this area is limted to animal responses. We designed experiments specifically aimed at measuring correlation, or what we conceive as possibly a rudimentary capacity of conceptual understanding. There was significantly improved performance after administration of the drug, but we do not know whether we shall find similar positive responses from humans. Even conservative extrapolations from experimental animals to humans are risky.

ANother area that has not been discussed is one of much concern: learning disabilities. With so many different causes underlying disabilities, no generalizations can be made. Where there is anatomical damage, the prognosis for benefits from PRL-8-53 would not be good. In the case of chemical aberrations as the only cause of a learning disability, any possible drug effect would depend on the nature of the aberration. Drug effects must be investigated for each type of disability; only experimentation will bring answers.

In summary, it appears that a number of important parameters of intellectual function are amenable to drug action. Improvement does ot seem limited to the young; the older group actually experienced a greater relative improvement in the test. However, just as the extent of improvement varied from one group to another, so did the response from one individual to the next. This is to be expected. The drug seems to augment some weak link in the chain of events related to intellectual function. This link is weaker for some than for others. The individual net effect is not predictable and will vary. We certainly are not dealing with a compound that would act as a great equalizer. Although some people with quite different base levels of performance might end up in close proximity, others will still be apart in performance. The important thing is that, regardless of initial performane level, improvment can still be achieved.

Finally, let us emphasize that we are dealing with an experimental compound; much investigation will be neccessary and many questions must be answered. So, while there is hope for the "absent minded professor" as well as for the student, both must wait until all regulatory requirements are met -- and we hope -- this or a related compound becomes available for use in the improvement of learning.

NIKOLAUS R. HANSL is a neuropharmacologist at Creighton University, Omaha, Nebr. He holds the Ph.D. from the University of Vienna. ADELE B. HANSL is his wife and research associate. The research reported here is based on a clinical report made by the Hansls and Beverley T. Mead at the August 1979 meeting of the American Society for Pharmacology and Experimental Therapeutics.





Is anyone aware of this substance? I would be grateful for updated information as I have not been able to find any. All medical research documents are almost 20 years old. It looks like that research has stopped with no particular reason.

And from what I have read this substance works well and is non toxic. Correct me if I am wrong.

User is offlineProfile CardPM
Go to the top of the page
+Quote Post

Reply to this topicStart new topic
1 User(s) are reading this topic (1 Guests and 0 Anonymous Users)
0 Members:

 



Lo-Fi Version Time is now: 11th December 2017 - 01:11 AM


Home     |     About     |    Research     |    Forum     |    Feedback  


Copyright BrainMeta. All rights reserved.
Terms of Use  |  Last Modified Tue Jan 17 2006 12:39 am

Consciousness Expansion · Brain Mapping · Neural Circuits · Connectomics  ·  Neuroscience Forum  ·  Brain Maps Blog
 · Connectomics · Connectomics  ·  shawn mikula  ·  shawn mikula  ·  articles