tag:blogger.com,1999:blog-655962722302095847.post909813910940118851..comments2024-03-28T22:33:35.806+01:00Comments on Epiphany: Azosemide in Autism – ça marche aussi / it works tooPeter Lloyd-Thomashttp://www.blogger.com/profile/10173383229834614994noreply@blogger.comBlogger34125tag:blogger.com,1999:blog-655962722302095847.post-74153961263436460432021-12-07T09:06:52.813+01:002021-12-07T09:06:52.813+01:00I do not buy in that way, but a Doctor reader of t...I do not buy in that way, but a Doctor reader of this blog did confirm the availability and prices of several interesting Japanese drugs, including Azosemide, from a German International Pharmacy. In effect, whatever prescription drug is sold in Japan can be ordered in Germany, as long as you have a prescription. The drug does not have to be approved in Germany. If the German pharmacy then has to ship abroad, then they caution that there is the possibility of an issue with customs, which is not their risk, but the buyer's.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-46649612441227048482021-12-06T17:52:08.945+01:002021-12-06T17:52:08.945+01:00Peter, are you still able to obtain azosemide thro...Peter, are you still able to obtain azosemide through a German International Pharmacy?Unknownhttps://www.blogger.com/profile/02312209847373810908noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-11179803594136418082021-08-02T20:31:55.627+02:002021-08-02T20:31:55.627+02:00Thank you! We will trial it as soon as my son is ...Thank you! We will trial it as soon as my son is re-stabilized on his current medications (he had to go off them to get an EEG). We also got a referral to a mitochondrial disease clinic based on his genetic polymorphism, and I have a recommendation for a doctor there who is open-minded about these things, so I am hopeful there. Sarahttps://www.blogger.com/profile/03931285116861266625noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-90412741298881144372021-07-28T22:23:38.156+02:002021-07-28T22:23:38.156+02:00I think it will be similar, give or take a week or...I think it will be similar, give or take a week or two.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-62586780334626382832021-07-28T20:25:52.779+02:002021-07-28T20:25:52.779+02:00Peter, would you think that Azosemide would take a...Peter, would you think that Azosemide would take about the same amount of time to show an effect as bumetanide?Sarahttps://www.blogger.com/profile/03931285116861266625noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-52038758528315086552021-05-17T10:02:01.582+02:002021-05-17T10:02:01.582+02:00Riza, Azosemide works in exactly the same way as b...Riza, Azosemide works in exactly the same way as bumetanide, it very slowly lowers the level of chloride inside neurons. All the research is on bumetanide and this is really the one to try first. <br /><br />Both drugs will take time to show any benefit. In my son Bumetanide took 10 days; in some people it can be 3 weeks. The researchers suggest trying a full 2 months before giving up, if there is no benefit.<br /><br />Azosemide has the advantage over bumetanide in that it causes much less diuresis.<br /><br />The smaller the dose, the smaller the effect on chloride and there may never be a big enough effect to change behavior and raise cognitive function.<br /><br />I would suggest taking one 60mg pill a day and hope that 20 days is long enough to get a response.<br />Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-88330041043345861222021-05-16T10:53:06.782+02:002021-05-16T10:53:06.782+02:00Peter,
I got the Azosemide 60mg
My son is 9 50lbs...Peter,<br /><br />I got the Azosemide 60mg<br />My son is 9 50lbs<br />What's the best dose to start please <br />30 or 60<br /><br />(Wish I can start with 30mg as I only got 20 pills for trial.)Rizahttps://www.blogger.com/profile/17553698982629217172noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-5869591065267804972020-02-21T16:38:55.038+01:002020-02-21T16:38:55.038+01:00about 8 monthsabout 8 monthsPeter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-31954517792267573832020-02-21T16:25:49.216+01:002020-02-21T16:25:49.216+01:00Hi Peter
How long has your son been taking the azo...Hi Peter<br />How long has your son been taking the azosemide?<br /><br />MKAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-10247131544762482772019-09-25T09:42:55.758+02:002019-09-25T09:42:55.758+02:00Vicky, the experiences I have had to date suggest ...Vicky, the experiences I have had to date suggest it is better to have a larger single daily dose than to have 2 small doses.<br /><br />For most people the only side effects of azosemide/bumetanide are ones causes by the diuresis. So it is the diuresis that limits the dosage you can give.<br /><br />In my son the more bumetanide/azosemide the better/bigger the effect is.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-21563938063755684202019-09-24T23:39:38.456+02:002019-09-24T23:39:38.456+02:00Hi Peter
I am 3 weeks into trial on my 4 yr old s...Hi Peter <br />I am 3 weeks into trial on my 4 yr old son and 30mg Azosemide looks good so far and no duresis at all.<br />Can see some subtle changes but will trial for 3 months and then see if it's working and if there are any significant gains..<br />Is it a good idea to give one 30 mg dose or split in twice a day ?<br /><br />VickyAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-30016304653885934332019-07-30T01:16:15.576+02:002019-07-30T01:16:15.576+02:00No, there was not specified type of zinc supplemen...No, there was not specified type of zinc supplement. <br /><br />Another excellent paper about DAT from danish group, which is collaborating with US researchers from the latest DAT paper :<br /><br />https://www.ncbi.nlm.nih.gov/pubmed/29559554<br /><br />There is also a lot about Zinc effects on DAT. Interestingly, in WT-DAT Zinc acts in a similar way like Ritalin, as reuptake inhibitor. But in some mutated DAT effect change from inhibitory to activatory, and therefore is Zinc partially restoring defect functions of mutated DAT. Problema is that it does not happen in every mutation, only in some of them - so you have to know exactly which one you have and also if this mutation was previously tested on Zinc effect. <br /><br />I am in contact with both reseacher groups right now / US and Denmark /, lets see what I can find out. Renehttps://www.blogger.com/profile/12238833363220684352noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-9586148806961085332019-07-29T17:54:19.991+02:002019-07-29T17:54:19.991+02:00Was there any particular type of zinc that improve...Was there any particular type of zinc that improved symptoms, or was any form of easily digestible zinc recommended?Tylernoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-37445278518395896822019-07-27T20:47:18.659+02:002019-07-27T20:47:18.659+02:00Even the prescription drugs have only a modest imp...Even the prescription drugs have only a modest impact on NKCC1/KCC2. In the lab some natural substances do have some effect, but in reality I think they will have a trivial impact. One is Ginseng.<br /><br />In some people with severe autism lowering chloride levels has a profound impact shifting them away from profound MR/ID. So I think it is well worth the struggle to obtain bumetanide or azosemide, just in case the person is a responder.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-59577515784710085042019-07-27T20:30:23.865+02:002019-07-27T20:30:23.865+02:00Tyler, your excellent comment and this new study h...Tyler, your excellent comment and this new study has mixed my day(s) completely...<br /><br />Just one little correction - with specific DAT blocker / ACT-01 / they were able to improve only one symptom in mutated mice / not symptoms / and it was hyperlocomotion. Other social and repetitive behaviors were not improved. And they conclude that it was done only by preventing the DA efflux through the mutated transporter into the synapse. <br /><br />This study is very important for me and my son, because we have done 3 years ago genetic testing through 23andme and he has a mutation in the SLC6A3 gene / rs28363168 /, which codes the dopamine transporter. I just was not able to find if his mutation is one the known mutations / besides the A559V / rs28364997 / which is linked to ADHD - so this one he does not have for sure /. There are no other rs numbers to find...at least I was not able to find any. <br /><br />After we found out his SLC6A3 mutation we have tried RITALIN / methylphenidate, Dopamine reuptake inhibitor / and had to stop it after 6 days. It caused worsening in almost every autistic symptom. As you wrote Tyler - at that time we probably did the opposite... <br /><br />We tried for several months also the ASD popular ketogenic diet and it ended in our case as disaster too...<br /><br />Although this failed interventions were very hard to digest for us, they gave us now extremely valuable informations. <br /><br />The same group of researchers did 2015 also this study : <br /><br />https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349303/<br /><br />and they found out in vitro that the functions of mutated DAT transporter - in the case of Y355A mutation DA uptake and in the case of T356M mutation both DA forward and reverse transport, were partially restored with Zinc. <br /><br />In my eyes the best cast scenario would be if his mutation would cause just a defect of Dopamine Re-Uptake from the synapse. In my current understanding the defect in Dopamine efflux into the synapse is more associated with ADHD symptoms and these he definitely does not have. <br /><br />The too high brain dopamine levels could be than targeted by BCAAs therapy, zinc supplementation and by partially restricted dietary intake of high proteine foods. Thats my theory right now. <br /><br />Thanks for every opinion !!!<br />Renehttps://www.blogger.com/profile/12238833363220684352noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-29970418402228745752019-07-27T15:33:33.116+02:002019-07-27T15:33:33.116+02:00Hi Tyler, hope your sons are doing well, thanks fo...Hi Tyler, hope your sons are doing well, thanks for this study about dopamine. As DAT blockers are strong prescription meds, could the problem be solved by taking BCAAs with something that increases intracelular presynaptic dopamine? And what could be?<br />ValentinaAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-74560630946008711292019-07-27T14:49:58.488+02:002019-07-27T14:49:58.488+02:00Are there any natural diuretic supplements that ha...Are there any natural diuretic supplements that have similar effects in balancing NKKC1/KCC2 towards NKCC1 for those who have difficulty obtaining a prescription/ordering online? Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-8185133727300766332019-07-25T10:34:48.866+02:002019-07-25T10:34:48.866+02:00A very interesting study on dopamine issues and au...A very interesting study on dopamine issues and autism came out today:<br /><br />Press Release:<br /><br />https://www.sciencedaily.com/releases/2019/07/190723182249.htm<br /><br />Paper:<br /><br />https://www.jci.org/articles/view/127411<br /><br />The study centered around a de novo mutation in a child with autism whereby the dopamine transporter protein (DAT) was mutated in such a way as that it both failed to do its primary job properly (recylcing dopamine by clearing it from the extracellular space and returning it to the pre-synaptic neuron), as well as aberrantly pumping intracellular dopamine from the presynaptic neuron, rather than pumping extracellular dopamine back into the presynaptic neuron. Both problems promote hyperdopaminergia at the synapse for both the pre-synaptic neuron and post-synaptic neuron, not to mention the pre-synaptic neuron runs out of dopamine for phasic release. On top of that, the increased levels of extracellular dopamine desensitize D2R receptors which leads to decreased dopamine synthesis in the presynaptic neuron, thereby decreasing proper phasic dopamine signaling and instead a situation where you have a noisy dopamine signal from the excess dopamine in the extracellular space with no phasic dopamine bursts coming from intracellular pre-synaptic sources, thereby leading to big deficits in reward learning.<br /><br />Now this is just one de novo mutation, but the really important thing here is the researchers found a gene in a human that caused autism and then put it into a mouse and produced autism symptoms, rather than the typical situation where researchers toy around with a bunch of genes in mice and find one that causes "autism symptoms", but then often does not do anything substantial in humans.<br /><br />Last but not least, the researchers improved symptoms in the mutant mice with a DAT blocker (not to be confused with a DAT Reuptake Inhibitor which in effect does the opposite of what would be intended with a DAT blocker).<br /><br />Therapeutically, reducing excessive extracellular dopamine levels via BCAA's or other therapies to reduce dopamine synthesis in the brain may solve half of the problem with this specific de novo mutation, but it likely won't restore phasic dopamine release because the mutant DAT protein will still be pulling dopamine out of the pre-synaptic neuron, rather than pushing dopamine back in as it is supposed to function. In that case I suppose you would need to increase dopamine levels somehow in the pre-synaptic neuron, while decreasing extracellular dopamine which makes BCAA therapy have the problem of both reducing extracellular as well as intracellular presynaptic neuron dopamine (which predominantly comes from the substantia nigra).Tylernoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-40417657971094120562019-07-25T08:43:01.255+02:002019-07-25T08:43:01.255+02:00Peter has discussed both in length in previous blo...Peter has discussed both in length in previous blog posts. <br /><br />Go to Google and type this as it should help narrow your search:<br /><br />vasopressin "site:epiphanyasd.blogspot.com"<br /><br />progesterone "site:epiphanyasd.blogspot.com"Tylernoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-1347118108533033772019-07-24T16:30:43.656+02:002019-07-24T16:30:43.656+02:00Have you already studied about Vasopressin and reg...Have you already studied about Vasopressin and regulation of testorerone precurssors?Arqueira do Tempohttps://www.blogger.com/profile/02947602648273815651noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-37202962873384454612019-07-22T13:52:37.199+02:002019-07-22T13:52:37.199+02:00I am still looking at what works best in our case....I am still looking at what works best in our case. Both Bumetanide and Azosemide "work". The optimal therapy may vary from person to person, because the diuresis varies from person to person.<br /><br />That is the only online pharmacy selling Japanese drugs, last time I looked they did not have Azosemide. They have the 50% cheaper generic as well as the more expensive Diart version.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-50956226840072232642019-07-22T13:30:49.248+02:002019-07-22T13:30:49.248+02:00Peter have you now dropped bumetanide completed fr...Peter have you now dropped bumetanide completed from the poly pill and are just giving azosemide twice a day or combination of both .<br /><br />PS their is one online pharmacy that carries azosemide without prescription <br />http://www.mimaki-family-japan.com/<br /><br />Can't guarantee this �� percent legit but this pharmacy is considered one of the more trusted online pharmacyAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-36755430264899257182019-07-22T09:35:24.120+02:002019-07-22T09:35:24.120+02:00Tyler, if you look up schizophrenia rather than au...Tyler, if you look up schizophrenia rather than autism you will find some references to glial tonic inhibition, but not much.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-40920603556795323962019-07-21T21:02:44.976+02:002019-07-21T21:02:44.976+02:00I was reading a bit about some neuroscience stuff ...I was reading a bit about some neuroscience stuff concerning the cerebellum and Purkinje cells and came across an idea mentioned in one of the papers I was reading called "glial tonic inhibition". So I looked into this topic and found the idea very interesting and possibly another vector to look into with respect to autism. Here is one recent paper concerning the subject:<br /><br />Paper:<br /><br />https://www.pnas.org/content/115/19/5004<br /><br />There are many links to immune support cells in the body and the brain being compromised in critical periods in-utero for various reasons (low-grade inflammation from obesity, viral infection, maternal antibodies, etc.) and autism. Also of course excessive serotonin from the mother (usually a sign of peripheral inflammation) can change the immune profile of the baby as well.<br /><br />There has been plenty of research into brain immune cells, especially microglia, possibly having a deleterious effect on brain function by either not pruning synapses effectively (autism) or pruning too many for too long (schizophrenia), but this is the first time I have read about glial cells having a direct inhibitory effect via GABA synthesis and release directly onto GABA receptors (the paper above concerns GABA-A receptors and granule cells which are exclusive to the cerebellum and also happen to be the most abundant cell type in the brain by number).<br /><br />Peter have you come across "glial tonic inhibition" before because I have not, and if you have are you aware of any autism research being done currently that investigates "glial tonic inhibition" with respect to autism.Tylernoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-34723127261878782822019-07-21T18:14:13.505+02:002019-07-21T18:14:13.505+02:00Hi Clare,
I don't know how old is your son, b...Hi Clare,<br /><br />I don't know how old is your son, but I really think it is a good idea to check blood potassium if you consider increasing the Bumetanide dose. One thing is just safety, but also some good effects of Bumetanide may be missed if a child's potassium level is not optimal. It is a very cheap test if you use private lab.<br /><br />My son has been on Bumetanide since he was 7 and indeed at the beginning the benefits were subtle so that the other Peter's blog reader saw my personal notes and concluded that Bumetanide effects are not really significant. <br />Over the years all interventions targeting chloride neuronal regulation helped my son to learn many things. This would not be possible without treatment, he started with moderate ID diagnosis as well. <br /><br />I wonder if Azosemide effect on potassium loss is similar to Bumetanide. <br /><br /><br />Agnieszka Wroczyńskahttps://www.blogger.com/profile/04738535364585304041noreply@blogger.com