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Cerebrolysin Nasal Spray

cerebrolysin

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#1 AuralAnomaly

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Posted 05 August 2013 - 02:31 PM


WARNING: It should be noted that two people from this board ("Krabby" and "PlasticPerson") have already reported serious and long term and/or permanent side effects to Cerebrolysin Nasal Spray. Their side effect claims can be found here: 
 
 
 
Please take time to thoroughly investigate before doing anything to your body!

 

 

 

Attached are PDFs with data from studies demonstrating efficacy of Cerebrolysin via intranasal administration, showing greater concentration within the CNS and less binding to peripheral tissues.

From the papers:

Tissue concentrations of 125I-Cerebrolysin peptides were measured in rats by quantitative gamma counting at 35 minutes after intravenous administration of a mixture of labeled and unlabeled Cerebrolysin (average 0.79 mg [110 µL] and 35.24 µCi]) (41). Mean concentrations of 125ICerebrolysin were 4501 ng/g in blood, ranged from 170 to 224 ng/g in tissue in brain regions and from 188 to 329 ng/g in spinal cord tissue, and were much higher in peripheral organs (41). After its intranasal administration, however, Cerebrolysin concentrations were greater in CNS regions (particularly in the hippocampus, septal nucleus, frontal cortex and olfactory bulb) and lower in peripheral tissues (41).


..comparison of intravenous vs. intranasal administration of Cerebrolysin in 10 rats demonstrates greater delivery to the CNS with intranasal delivery (p0.01) and greater delivery to the peripheral organs and blood with intravenous delivery (p0.01). On average, intravenous blood concentration were 6.8 times greater than intranasal blood concentrations. Five CNS tissues were collected and counted including ventral brain dura, dorsal brain dura, optic nerve, trigeminal nerve, cervical spinal cord, olfactory epithelium, deep cervical lymph nodes and common carotid had significantly greater delivery following intranasal administration than intravenous delivery (p0.01). All peripheral tissues (except superficial lymph nodes, esophagus, and trachea) had significantly greater concentration following intravenous delivery (p0.01). Conclusions:Overall, these results demonstrate significantly greater delivery to the brain following intranasal administration of Cerebrolysin. Intranasal Cerebrolysin is directly delivered to the brain along the olfactory and trigeminal pathways. Intranasal administration of Cerebrolysin will provide a non-invasive method to treat Alzheimer’s disease and stroke patients by providing larger drug concentrations to the brain and minimal concentrations to the peripheral organs.


This should be good news to those unwilling to inject themselves over fear of needles or glass particles or formation of scar tissue. Simply dump your Cerebrolysin in a nasal spray bottle and get squirting.

Have fun!

Attached Files


Edited by cryonicsculture, 28 May 2014 - 12:23 AM.

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#2 formergenius

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Posted 05 August 2013 - 04:03 PM

These are intravenous vs. intranasal studies.. I remember reading something about how intramuscular is superior to oral, but how would intranasal compare to intramuscular? In any case, I'd prefer a nasal spray over a needle any day.

Nice find btw.

Edited by formergenius, 05 August 2013 - 04:04 PM.


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#3 Metagene

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Posted 05 August 2013 - 06:33 PM

Awesome! I really don't mind needles but this way is fast and effective.

#4 meatsauce

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Posted 05 August 2013 - 07:10 PM

I was just about to post this info. I just got a nasal spray bottle and will be trying it this way!

#5 Nattzor

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Posted 05 August 2013 - 08:06 PM

Hmm, haven't read the long thread about cerebrolysin yet (about to), but what is the dosage and cost?

#6 AwesomeName

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Posted 05 August 2013 - 08:54 PM

Wouldn't you have to spray a lot of it to get it to work?

#7 AuralAnomaly

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Posted 05 August 2013 - 10:04 PM

Personally I think the superior efficacy of intramuscular over intravenous administration is due to extended plasma concentrations. By spraying multiple times throughout the day we could easily extend the duration and also keep levels relatively constant for as long as we wish.

If the standard spray bottle ejects around 0.1 ml per squirt, that's 100 squirts per 10 ml ampoule, which could last 10 days if sprayed once every hour over a 10 hour period. Would that work, probably, but whether 1 ml per day concentrated into the brain intranasally over a longer period is more or less effective than say 5 ml leaked slowly into systemic circulation intramuscularly is the sort of thing we would like to find out!
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#8 Healthy Tony

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Posted 05 August 2013 - 11:31 PM

I was just about to post this info. I just got a nasal spray bottle and will be trying it this way!

Are you currently taking Cere. and have you in the past? What dosage/ dosing protocol will you be using for this experiment?

Please post you results here when you do end up trying this out, as I am sure a lot of members are eagerly awaiting first hand reports on this route of administration.

#9 meatsauce

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Posted 06 August 2013 - 12:46 AM

I have taken from 1 to 5 ml a day and am currently taking 1.5 ml a day. Ill try 1 ml internasal and see how strong the effects are vs 1 ml injection.

#10 Sholrak

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Posted 06 August 2013 - 04:15 AM

Theoretically:

Intravenous > Intamuscular > Nasal > Oral

Although, I have not tested IV, some theories maintain IM is better than IV because of some more extended in time mechanism. The majority say IV is more effective.

Now, we should see if nasal is more effective than IM, but it sounds promising. If I can get the 80% effectiveness of IM by nasal route, I would accept inmediately. And IM is not a big issue for me, but you need to worry about those glass particles and the risk of injecting too much repeatedly in the same spot and causing an scarring...

#11 umop 3pisdn

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Posted 06 August 2013 - 06:36 PM

I don't know what the ideal drop size would be in nm or whatever but I would imagine that some kind of atomizer would work better than the standard intranasal squeeze bottle. This website goes into the different systems for this ROA:

http://intranasal.ne...ues/default.htm

The Vianase and Optinose seem perhaps like the more advanced systems but neither seem to be on the market yet. There's also the LMA MAD system which you can buy, one version of which just attaches to the end of a syringe, and they also have a bottle atomizer (LMA MADomizer) where you would just empty the ampoule into the bottle and the pump would dispense a measured dose of 0.1mL. This system might seem a little better to me because the nozzle is on a long arm that you could bend to direct up into the nasal cavity better.

One thing I wonder about is the risk of contamination. The pumps themselves shouldn't carry any risk for contamination, but rather since the drug is peptides or whatever do you have to worry about an opened ampoule sitting in the fridge becoming contaminated? I know a lot of the concern is related to injections, but I would imagine that the nasal mucosa would be just as subject to infection.
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#12 semi-retarded-individual

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Posted 07 August 2013 - 04:02 AM

I know Cere is safe to inject intramuscularly, if done properly, but is the same solution safe to put into your nose? It's not going to harm the mucous membranes or tissues in any way, is it?

#13 AuralAnomaly

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Posted 07 August 2013 - 08:49 AM

Those spray atomizers look incredible! I'll be looking into that more for sure. For now maybe a simpler cheaper way to avoid contamination to some extent is to simply decompress the spray ejector only after pulling it out from the nasal passages and wiping the tip with an alcohol swab?

There's an additional option I've considered. The linear polysaccharide Chitosan is an antibacterial preservative, and also a powerful membrane permeability enhancer. The following study demonstrated the addition of medium viscosity Chitosan to BDNF nasal spray increased intranasal bioavailability by around 13 fold:

PURPOSE:
To investigate the plausibility of delivering brain-derived neurotrophic factor (BDNF) to brain via nose-to-brain pathway using chitosan as barrier-modulating agent.
METHODS:
Effect of different viscosity grades chitosan at different concentrations on permeation of fluorescein isothio-cyanate dextran (FD 40 K) across bovine olfactory mucosa was studied using Franz diffusion cells. Medium viscosity chitosan was used to carry out permeation studies of BDNF. Pharmacokinetic and pharmacodynamic studies were carried out in Sprague dawley rats upon intranasal/i.v administration of different formulations.
RESULTS:
Medium viscosity chitosan more efficiently enhanced permeation of FD 40 K across olfactory mucosa compared to other grades. In case of BDNF, medium viscosity chitosan (0.25% w/v) enhanced permeation ~14-fold over control (18.78 ± 16.69 ng/cm(2)). Brain bioavailability of rats administered intranasally with BDNF solution containing chitosan was significantly enhanced ~13-fold compared to rats administered with same concentration of BDNF solution without chitosan. In rats subjected to immobilization stress, BDNF solution containing chitosan significantly decreased immobility time.
CONCLUSIONS:
Intranasal formulations containing chitosan as barrier-modulating agent significantly enhanced brain bioavailability of BDNF

http://www.ncbi.nlm....pubmed/21879386

So that's one possible way of increasing bioavailability even further and keeping contamination at bay. But I can't find any data as to whether the addition of such things could in any way compromise the stability of peptide chains in solution. Someone help us out here..

I couldn't find anything to suggest any kind of damage to the mucous membranes, but I am a little worried about the possible interactions of Cerebrolysin's IGF-1 content and nasal and surrounding tissues of the face. It might rejuvenate the face and nose a little.. It might turn us into circus freaks. Preliminary Googling on IGF-1 on skin and cartilage suggests the former :)

#14 sunshinefrost

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Posted 07 August 2013 - 05:03 PM

Very cool ! Did ebewe come out with an actual customized atomizer or did someone simply snorted an ampoule ?

#15 semi-retarded-individual

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Posted 07 August 2013 - 08:39 PM

So is anyone in this thread actually going to try this?

Also: what is the best source for Cerebrolysin?

#16 meatsauce

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Posted 08 August 2013 - 04:21 PM

I got a nasal spray bottle that sprays a mist pretty good. What I do is draw the ampule of cerebrolysin into two 5ml syringes and then dispense 1 ml of cerebrolysin into the container. I have had to add a little extra water in order for the hose to suck up properly and create a good spray. The unused cerebrolysin can be stored in the syringe.

For administration you have to aim the nozzle into the nasal passage and cover the other nostril with your finger and snort in the cerebrolysin while you spray. You know you did it right when you feel a weaker sensation of getting water up your nose.

I feel a sensation of a calm mental clarity soon after administration, similar to coming out of a meditation session. I was reading that cerebrolysin has an effect on the gaba-b receptors so this might be part of it.

Its hard to tell how long those effects last right now because I am also taking a 1mg dose of hydergine almost everyday now which is working out pretty well, but I think the initial effects fade in strength but you still feel beneficial effects for a few hours. The long lasting effect might not be something that we "feel" strongly though.



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#17 cyberger

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Posted 08 August 2013 - 04:48 PM

So is anyone in this thread actually going to try this?

Also: what is the best source for Cerebrolysin?


Reading through the 55 Page Cerebrolysin thread, it looks like there are 2 recommended/trusted sources (with Nootropic.eu being the most recommended):

http://nootropic.eu/ $45.34 for 5 x 5ml pack with $11.20 shipping and tax
http://www.gerovitalshop.eu $46.77 for 5 x 5ml pack with $25 estimated flat rate shipping

Incidentally, the GerovitalShop also sells the 10 x 1ml Pack which for $38.74; the smaller 1ml size is probably better for a nasal spray, to avoid contamination by having extra unused product.
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#18 cyberger

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Posted 08 August 2013 - 06:25 PM

Also, another abstract in the PDF @AuralAnomaly posted indicates that INTRANASAL Cerebrolysin is SAFE and EFFECTIVE in humans.

Summary: In a placebo-controlled experiment with ischemic stroke patients, 15 patients were given 1ml cerebrolysin administered INTRANASALLY for 7 days with clinically significant improvements and no adverse events.


Effect of Intranasal Administrated Cerebrolysin on Ischemic Stroke
X. Liu, G. Xu, W. Zhu, X. Fan

Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China

The present study was aimed at investigating in patients with ischemic stroke influence of Cerebrolysin infusions on cognitive performance, clinical outcome and electrophysiological results.

SUBJECTS AND METHODS: Thirty patients were randomized into two groups. All patients receive standard management according to the established ischemic treatment guidelines. In addition, 15 patients receive intranasal administrated Cerebrolysin in dose of 1 ml for 7 days shortly after the onset of the ischemic stroke. The other 15 patients received same dosage of normal saline as placebo.

RESULTS: A decrease in slow electroencephalogram activity and an increase in fast frequencies were observed after the administration of Cerebrolysin. This electrophysiological effect was not influenced by stroke time course or severity, or by the chronic treatment with other neuroprotection agents. Cognitive performance, evaluated with Mini-mental state examination (MMSE), improved in ischemic stroke patients after Cerebrolysin treatment, independent of disease severity, time course or disability. A significant improvement in the patients’ clinical outcome, only evident during the first year after the onset of stroke was also detected following Cerebrolysin infusions. No relevant changes in biological parameters nor drug-related adverse events were observed.

CONCLUSION: These promising preliminary results suggest that intranasal Cerebrolysin might be a useful treatment to improve the recovery of patients with ischemic stroke, and encourage the conduction of confirmatory clinical trials.


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#19 AuralAnomaly

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Posted 08 August 2013 - 10:09 PM

I'll second Nootropic.eu as the preferred source, having dealt with them before I'd highly recommend their services. Plus there's a special offer on atm for longecity members if you guys check the main Cerebrolysin thread :)

Looking forward to seeing more of peoples experiences with this ROA!

Edited by AuralAnomaly, 08 August 2013 - 10:12 PM.


#20 semi-retarded-individual

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Posted 09 August 2013 - 02:45 AM

I'll second Nootropic.eu as the preferred source, having dealt with them before I'd highly recommend their services. Plus there's a special offer on atm for longecity members if you guys check the main Cerebrolysin thread :)

Looking forward to seeing more of peoples experiences with this ROA!


Well now I simply have no excuse! :)

Edit: Damn.... the voucher expired on 7/21/13




Does anyone know which nasal sprayer they will be using?

Edited by semi-retarded-individual, 09 August 2013 - 03:01 AM.


#21 cyberger

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Posted 09 August 2013 - 03:07 AM

I'm looking for a quality nasal sprayer (or 'atomizer') too. Dr. Tim Wolfe, who runs the comprehensive intranasal delivery website http://www.intranasa...nks/default.htm, invented the "MAD - mucosal atomization device." He's since sold the idea to another company, and this is the companies product page for the MAD: http://www.lmana.com....php?pwpID=6359.

This post describes a paramedic giving Intranasal Fentanyl (http://medicscribe.c...nasal-fentanyl/) and one comment says the device used in the post is the: "LMA MAD Nasal by Wolfe Tory Medical. I think they are about $1 each. They screw on the end of a syringe. They work great."

Amazon sells the MAD with a syring for $5.95 + $5.00 Shipping: http://www.amazon.co...words=mad nasal and although they are supposed to be a single-use device, a comment on the product page says someone is doing intranasal colloidal silver and they re-use it instead of throwing it out.

What are people's thoughts about re-using the atomizer? Would there be a way to clean it out sufficiently for re-use? Or a cheap place to buy in bulk? Or are there other devices people recommend?

Edited by cyberger, 09 August 2013 - 03:16 AM.

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#22 sunshinefrost

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Posted 09 August 2013 - 03:31 AM

I would use an atimiser with a disposable tipp, if it exists... or an atomizer that doesnt allow back wash in the container. Would you store the atomiser back in the fridge ? I've never kept opened ampoules longer than 3 days, with this technic it would probably involve keeping it for a few more days

#23 semi-retarded-individual

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Posted 09 August 2013 - 04:25 AM

I personally wouldn't worry about re-using the atomizer. Can someone explain what the concern is? What would happen if after use, you either immersed it in hydrogen peroxide or rubbing alcohol to disinfect and then put it on a shelf to dry?

#24 AuralAnomaly

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Posted 09 August 2013 - 10:19 AM

Oh man I have to buy that.. Should we be worried about spray atomizers damaging peptide chains? Like, I remember reading IGF-1 is so sensitive to physical shock you couldn't even shake its solution in a vial :|o
Even if that's the case there could be some trade off for increased surface area vs intact peptides at the membranes. We should test for all this!

Re-use after immersion in rubbing alcohol sounds good to me too. Or maybe boiling water if alcohol corrodes the plastic.

edit: LMA's own FAQ http://www.lmana.com....php?pwpID=6557 says the MAD nasal can't effectively be sterilized for reuse. But, they would say that ;)

They have another spray atomizer called the MADomizer that looks more like a conventional spray applicator and is designed for minimal contamination and reuse. The dose isn't adjustable like the MAD Nasal, it's fixed at 0.1 ml per spray. See here: http://www.lmana.com....php?pwpID=6549

Also check out their clinical evidence portal. Might find something interesting! http://lms.doctorevidence.com/

Edited by AuralAnomaly, 09 August 2013 - 11:13 AM.

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#25 vlk

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Posted 09 August 2013 - 03:40 PM

Very interesting, I will have to try this.

The MADomizer does look like the best option out there for sterility and accurate dosing, although it looks like they just dripped it slowly into each nostril in the study.
Of course, you would still need to make sure you deliver only a small amount at a time, or you'd just be wasting the stuff by pouring it down the back of your throat!


Also check out their clinical evidence portal. Might find something interesting! http://lms.doctorevidence.com/


AuralAnomaly, how does one get access to this?


Edit:

Having done a little more research, I see no reason why an atomizer would actually be needed apart from convenience.

The main problems affecting intranasal delivery via drops are mostly related to patient cooperation, and I'm assuming that won't be a problem for self administration!

There is a good summary of information at intranasal dot net if anyone is interested, this diagram of the recommended head positions is from there:
Attached File  Merkus head position.JPG   90.78KB   14 downloads

Edited by vlk, 09 August 2013 - 03:57 PM.


#26 AuralAnomaly

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Posted 09 August 2013 - 03:56 PM

Right so, I checked out all the options everyone's suggested so far. I agree MAD Nasal seems to be the easiest and cheapest. This site is worth checking http://www.vitaid.co...d21eabe0dc04688. It can administer 0.5 ml into each nostril before dripping back into the throat, so if dosing at that level it's likely you'll get through a whole syringe before any contaminants could wriggle back into the solution and cause problems. There's no reason to think you couldn't disinfect the tip for reuse before that could happen, either. Their UK distributors sell to individuals in bulk boxes of 25, I'll post up prices soon. For other countries check LMA's website.

Yet another way to increase bioavailability even more (lol), courtesy of the "How it Works" videos for the OptiNose @ http://www.optinose.com/; exhaling through the mouth as the spray is applied widens the nasal valve and pushes back the soft palate, closing the nasal cavity off from the throat, thus allowing the mist to recirculate and maximally coat the nasal membranes.

Sorry about that, figured there would be a registration button for new users! IIRC you can register here http://www.lmaco.com/cp1.php

Edited by AuralAnomaly, 09 August 2013 - 04:22 PM.


#27 cyberger

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Posted 09 August 2013 - 05:15 PM

Having done a little more research, I see no reason why an atomizer would actually be needed apart from convenience.


http://www.intranasa...es/default.htm:

"The efficacy of the nasal dropper techniques varies depending on which author you read. Some authors find drops to be an effective method of delivery,[1-3] while others note poor surface area coverage and rapid removal of the medication into the throat via runoff and ciliary movement.[1, 4-10]


Also, the attached picture shows better blood concentration for a spray vs. drops.

Maybe I (or someone else), can try both techniques and report back.

Attached Files


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#28 vlk

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Posted 09 August 2013 - 05:17 PM

I just tried dripping 0.2ml per nostril, "praying to Mecca" position, and stayed in that position for about 1 minute after. There was still a very small amount dripping into my throat when I stood up after (i.e just enough to taste the cerebrolysin).

In that case, with up to 0.5ml doses the atomizer would definitely be superior to intranasal dripping. Apologies if my last post was misleading.

Also, the attached picture shows better blood concentration for a spray vs. drops.


That could also be important, however I'm not sure how much effect it would have with cerebrolysin, as some drugs show almost exactly the same serum concentration vs time curves for both intranasal (IN) and intravenous (IV) administration. Cerebrolysin however shows much higher concentrations with IN, perhaps due to crossing the BBB directly through the olefactory canal. (I'll add links to the papers if I can find them again)

I was just playing devil's advocate, pointing out that atomization might not be needed as it wasn't used in the studies :)
It would almost certainly be equal to or better than dripping though, and it looks like much higher doses could be used too... I think I'll have to get some atomizers now and do a proper comparison!

Edited by vlk, 09 August 2013 - 05:32 PM.

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#29 Healthy Tony

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Posted 09 August 2013 - 06:47 PM

I just tried dripping 0.2ml per nostril, "praying to Mecca" position, and stayed in that position for about 1 minute after. There was still a very small amount dripping into my throat when I stood up after (i.e just enough to taste the cerebrolysin).

In that case, with up to 0.5ml doses the atomizer would definitely be superior to intranasal dripping. Apologies if my last post was misleading.

Also, the attached picture shows better blood concentration for a spray vs. drops.


That could also be important, however I'm not sure how much effect it would have with cerebrolysin, as some drugs show almost exactly the same serum concentration vs time curves for both intranasal (IN) and intravenous (IV) administration. Cerebrolysin however shows much higher concentrations with IN, perhaps due to crossing the BBB directly through the olefactory canal. (I'll add links to the papers if I can find them again)

I was just playing devil's advocate, pointing out that atomization might not be needed as it wasn't used in the studies :)
It would almost certainly be equal to or better than dripping though, and it looks like much higher doses could be used too... I think I'll have to get some atomizers now and do a proper comparison!

Could you please tell us if you were able to subjectively note any effect from your small intranasal dosage?

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#30 vlk

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Posted 09 August 2013 - 07:09 PM

More info:

It seems that some drugs when taken intranasally show similar plasma and CSF concentration curves to IV administration.
They are simply absorbed into the blood stream. eg. Attached File  10.1023-B-PHAM.0000026431.55383.69.pdf   71.23KB   8 downloads

Others, however are absorbed directly through the olfactory neurons and into the CNS without going through the blood! Attached File  Carbamazepine uptake into rat brain following intra-olfactory transport.pdf   424.43KB   8 downloads
This is also what happens to cerebrolysin.

What would the best nasal delivery method be, given this information? At the moment I have no idea!
I have read about dripping, atomization and gels so far, but I don't know how they compare.

Adding a vasoconstrictor would probably help though, reducing the amount that is absorbed into the blood and therefore increasing the amount that goes directly into the brain:
Attached File  J Pharmacol Exp Ther-2009-Dhuria-312-20.pdf   323.26KB   4 downloads




Could you please tell us if you were able to subjectively note any effect from your small intranasal dosage?

I've taken about 4ml in total intranasally today, although I think 2-3ml of that went straight down my throat before I worked out how to do it properly.
After my last 0.4ml (0.2ml per nostril) I thought I felt a kind of "alert motivation" coming on very similar to when I took cerebrolysin intravenously. This could just be the placebo effect though, but I will be following this thread and if I do notice any reliable, repeatable effects, I will definitely report them here!





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