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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 5 of 5. This is the beginning of the thread.
Posted by PeterMartin on March 20, 2019, at 1:22:16
New study shows a novel drug that modulates inflammation in the brain might rapidly reduce depression. A google search shows this stuff is available as a research chemical so there's a chance some of the risky folk over at the https://www.longecity.org forums have already tried it. Off to search :)
Study:
https://medicalxpress.com/news/2016-03-chemical-tool-depression-therapy.html----
The research, published March 14 in the journal Proceedings of the National Academy of Sciences, involves studies of an inhibitor of soluble epoxide hydrolase in rodents. Soluble epoxide hydrolase, or sEH, is emerging as a therapeutic target that acts on a number of inflammatory or inflammation-linked diseases."The research in animal models of depression suggests that sEH plays a key role in modulating inflammation, which is involved in depression," said Hammock, a distinguished professor of entomology with a joint appointment at the UC Davis Comprehensive Cancer Center. "Inhibitors of sEH protect natural lipids in the brain that reduce inflammation and neuropathic pain. Thus, these inhibitors could be potential therapeutic drugs for depression."
Researchers from Hammock's laboratory, collaborating with depression expert Kenji Hashimoto and colleagues at the Chiba University Center for Forensic Mental Health, Japan, examined the role of the potent sEH inhibitor known as TPPU, in a rodent model of depression, "social defeat."
They found that TPPU displayed rapid effects in both inflammation and social-defeat-stress models of depression. Expression of sEH protein was higher in key brain regions of chronically stressed mice than in control mice, they found.
New therapeutic approach:
"Most drugs for psychiatric diseases target how neurons communicate; here we are targeting the wellness and environment of the neurons," said UC Davis researcher Christophe Morisseau.
In further explaining the significance of the findings, UC Davis researcher Karen Wagner said: "The rapid antidepressant action of the sEH inhibitor in these murine (mouse) models of depression is truly noteworthy because current antidepressants used in humans and animal models take weeks to have full effects."
The researchers also discovered that postmortem brain samples of patients with psychiatric diseases, including depression, bipolar disorder and schizophrenia, showed a higher expression of sEH than controls.
The researchers found that pretreatment with TPPU prevented the onset of depressionlike behaviors in mice after induced inflammation or repeated social-defeat stress. Mice lacking the sEH gene did not show depressionlike behavior after repeated social-defeat stress.
"All these findings suggest that sEH plays a key role in the pathophysiology of depression and that epoxy fatty acids, and their mimics as well as sEH inhibitors, are potential therapeutic or prophylactic drugs for depression," Hashimoto said.
Addresses a pressing need:
Robert E. Hales, distinguished professor of clinical psychiatry and the Joe P. Tupin Endowed Chair of the Department of Psychiatry and Behavioral Sciences at UC Davis School of Medicine, said new medication treatment approaches are needed to treat depression.
Hales, who was not involved in the research, said the new paper represents "an important and novel approach to treating depression."
"With lifetime prevalence rates of major depressive disorder being in the range of 16 percent and with nearly two-thirds of patients failing to respond to pharmacologic treatments, there is a pressing need to discover new medication treatment approaches," Hales said. "Their findings lend support to the potential use of TPPU, a sEH inhibitor, as a new therapeutic medication to prevent and treat depression."
Posted by PeterMartin on March 20, 2019, at 1:39:49
In reply to TPPU (sEH inhibitor) for depression: [New], posted by PeterMartin on March 20, 2019, at 1:22:16
Doesn't look like anyone tried TPPU but there was mention of one natural sEH inhibitor. Seems like it was going to be marketed as a sugar alternative but never got FDA approval as GRAS I guess. Not sure if you can buy it as a supplement or if would have any benefit even if so.....
https://www.longecity.org/forum/topic/85732-seh-inhibition/
Potent Natural Soluble Epoxide Hydrolase Inhibitors from Pentadiplandra brazzeana Baillon: Synthesis, Quantification, and Measurement of Biological Activities In Vitro and In Vivo
We describe here three urea-based soluble epoxide hydrolase (sEH) inhibitors from the root of the plant Pentadiplandra brazzeana. The concentration of these ureas in the root was quantified by LC-MS/MS, showing that 1, 3-bis (4-methoxybenzyl) urea (MMU) is the most abundant (42.3 μg/g dry root weight). All of the ureas were chemically synthesized, and their inhibitory activity toward recombinant human and recombinant rat sEH was measured. The most potent compound, MMU, showed an IC50 of 92 nM via fluorescent assay and a Ki of 54 nM via radioactivity-based assay on human sEH. MMU effectively reduced inflammatory pain in a rat nociceptive pain assay. These compounds are among the most potent sEH inhibitors derived from natural sources. Moreover, inhibition of sEH by these compounds may mechanistically explain some of the therapeutic effects of P. brazzeana.
full text https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319826/
Posted by PeterMartin on March 20, 2019, at 1:54:42
In reply to Re: TPPU (sEH inhibitor) for depression: [New], posted by PeterMartin on March 20, 2019, at 1:39:49
One more article from Jan 30 on this topic:
https://www.frontiersin.org/articles/10.3389/fphar.2019.00036/full
Role of Soluble Epoxide Hydrolase in Metabolism of PUFAs in Psychiatric and Neurological Disorders
---Many patients with depression become chronically ill, with several relapses or later recurrences, following initial short-term improvement or remission. Relapses occur at a rate of over 85 percent within a decade of an index depressive episode (Forte et al., 2015; Sim et al., 2015). Therefore, the prevention of relapse and recurrence is important in the management of depression. Taken together, it seems that sEH inhibitors could be prophylactic drugs to prevent or minimize relapses triggered by inflammation and/or stress in remitted patients with depression (Hashimoto, 2016; Ren et al., 2016). In addition, given the comorbidity of depressive symptoms in PD or DLB patients (Cummings, 1992; Takahashi et al., 2009; Goodarzi et al., 2016; Schapira et al., 2017), it is also likely that sEH inhibitors may serve as prophylactic drugs to prevent the progression of PD or DLB in patients.
Some natural compounds with sEH inhibitory action were reported. MMU [1,3-bis (4-methoxybenzyl)urea](Figure 2), the most abundant (45.3 μg/g dry root weight from the plant Pentadiplandra brazzeana), showed an IC50 of 92 nM via fluorescent assay and a Ki of 54 nM via radioactivity-based assay on human sEH (Kitamura et al., 2015). MMU is about 8-fold more potent than previously reported natural product sEH inhibitor honokiol (Lee et al., 2014; Kitamura et al., 2015; Figure 2). These findings may explain partly the pharmacological mechanisms of the traditional medicinal use of the root of P. brazzeana. Therefore, it is of interest to study whether the use of the root of P. brazzeana has beneficial effects in patients with psychiatric and neurological disorders.
Posted by porkpiehat on March 20, 2019, at 12:25:44
In reply to Re: TPPU (sEH inhibitor) for depression: [New], posted by PeterMartin on March 20, 2019, at 1:54:42
off topic, but how's the Marplan working for you?
Posted by PeterMartin on March 21, 2019, at 0:55:10
In reply to Re: TPPU (sEH inhibitor) for depression: [New] » PeterMartin, posted by porkpiehat on March 20, 2019, at 12:25:44
> off topic, but how's the Marplan working for you?
It's definitely helping in the way it usually does. I think I may have a bit of depersonalization that people seem to say it's especially effective for. It really makes me feel on point / "like myself" if that makes any sense. My focus is better.
That said I wouldn't say I'm great at the moment. I'm still only 22 days off Nardil and on Marplan (no washout). I've gone down from 250 to 100 on Topamax during that period as well so I could be going through w/d of either of those two + not being full on Marplan yet. I don't know.
I'm sorry I keep avoiding your req to chat one on one it just makes me anxious for some reason. I've learned a lot from your comments about Marplan and dosing (saying how you get irritable on higher dosages which I think I do as well but probably never admitted to myself). I'm not always in tune w/ how I feel so I just don't know if I'd be helpful in a one on one chat or possibly just trying to tell you what I think you'd want to hear - I know that sounds stupid but that's a problem of mine.
I wish there was something I could add for a little extra kick but I'm not sure what. I don't want to risk mania so I think my options are limited unless I ditch the Marplan and start all over....
I hope you are doing well!
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