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Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 25 of 29. This is the beginning of the thread.
Posted by Rosy Crucifiction on October 15, 2009, at 13:07:33
I'd appreciate any comments. This seems to be saying memantine (in mouse models) is a reversible MAO inhibitor. They hypothesize MAO inhibition in humans:
"Thus, it is plausible that peripheral administration of memantine may inhibit MAO activity in the human brain, as well as having effects through NMDA receptor antagonism."Influence of Memantine on Brain Monoaminergic Neurotransmission - Parameters in Mice: Neurochemical and Behavioral Study
Hiroshi ONOGI,aSeiichiro ISHIGAKI,bOsamu NAKAGAWASAI,*,aYumiko ARAI-KATO,cYuichiro ARAI,d,1) Hiromi WATANABE,aAtsushi MIYAMOTO,eKoichi TAN-NO,and Takeshi TADANO
"Memantine, a non-competitive antagonist of NMDA receptors, has recently been used in Alzheimers dis- ease. The influences of memantine on behavioral changes, monoamine oxidase (MAO) activity and reuptake of both serotonin (5-HT) and dopamine in mice were examined in the present study. Memantine dose-dependently increased locomotor activity. This effect was inhibited by intraperitoneal (i.p.) administration of haloperidol.
Furthermore, administration [intracerebroventricular (i.c.v.)] of memantine did not induce the head-twitch response (HTR). However, the 5-HT-induced HTR was potentiated by the combined administration of memantine.
The enhanced HTR was inhibited by i.p. administration of haloperidol or 5-HT2Aantagonist ketanserin. Memantine at 1mM inhibited both MAO-A and MAO-B activities in mouse forebrain homogenates to 37% and 64% of controls, respectively. LineweaverBurk plots analysis revealed competitive inhibition with both MAO-A and MAO-B. The inhibitions were also reversible. Memantine inhibited the reuptake of both 5-HT and dopamine into mouse forebrain synaptosomes. 5-HT and dopamine reuptakes were inhibited to 2% and 16% of controls, respectively, with 1mMmemantine. These findings suggest that the increased locomotor activity and enhanced 5-HT-induced HTR by memantine may result from the reuptake and turnover inhibitions of 5-HT and dopamine."download whole article here:http://www.jstage.jst.go.jp/article/bpb/32/5/850/_pdf
Posted by Rosy Crucifiction on October 15, 2009, at 13:14:53
In reply to Memantine as a reversible MAO Inhibitor?, posted by Rosy Crucifiction on October 15, 2009, at 13:07:33
It seems worth saying that memantine seems to have no reaction with tyramine and few drug interactions.
Posted by g_g_g_unit on October 15, 2009, at 17:43:03
In reply to Memantine as a reversible MAO Inhibitor?, posted by Rosy Crucifiction on October 15, 2009, at 13:07:33
hmm, i wonder what doses were used. maybe that's why some high do better on 40mg, etc.
Posted by Rosy Crucifiction on October 15, 2009, at 21:59:08
In reply to Re: Memantine as a reversible MAO Inhibitor?, posted by g_g_g_unit on October 15, 2009, at 17:43:03
I wondered the same thing. In addition (see below) because of memantine's long half life (60-80 hours) it may be that it just takes some people a long time to see MAO inhibition. I've emailed the folks at Merz about memantine as an MAO. I'll repost when I hear back. The authors had the following to say re: humans:
"Memantine is often administered to patients with Alzheimers disease; the doses administered are 20mg/d depending on the case.49)It is known that the plasma concentration of memantine reaches over 150ng/ml as Cmax following the administration of 20mg memantine to patients.50) This means that the plasma concentration of memantine might be above 0.7mM. Although memantine rapidly crosses the bloodbrain barrier,51) it is thought that this concentration might be too low to inhibit MAO activity.However, it is known that other monoamines such as 5-HT, DA and noradrenaline can be actively taken up into synaptosomes by the monoamine transporter where they are concentrated about 200-fold. In support of this report, we hypothesize that, in the brain, memantine may be concentrated in a similar manner and thereby reach effective concentrations. Thus, it is plausible that peripheral administration of memantine may inhibit MAO activity in the human brain, as well as having effects through NMDA receptor antagonism."
Posted by g_g_g_unit on October 15, 2009, at 23:08:03
In reply to Re: Memantine as a reversible MAO Inhibitor?, posted by Rosy Crucifiction on October 15, 2009, at 21:59:08
have you ever tried Memantine?
Posted by Rosy Crucifiction on October 15, 2009, at 23:22:02
In reply to Re: Memantine as a reversible MAO Inhibitor?, posted by g_g_g_unit on October 15, 2009, at 23:08:03
Yes. I'm currently taking:
memantine 15 mg. (start 20 next week)
wellbutrin xl 300 mg (brand - generic sucks)
concerta 72 mg (MUCH better than ritilin for me)
liorix 150 mg (150 mg t4 / 30 mg t3)
deplin
test. cypionate
I am MDD no psychosis, ADHD (inattentive), SAD and soft bipolar 2. The memantine has added real antidepressant effect and some hints of ability to experience pleasure. Titration has been tough for me. The first 3-4 days at 5 mg and at each 5 mg increase I have felt weak, strange, and like I couldn't handle the med. Within 4-5 days taht has changed to a real brightening of mood and a feeling of hopefulness. I now feel well enough to sign up for outpatient treatment at a depression center hospital (it's tough when you're too sick to deal with getting better). Anyway, the MAO bit is quite interesting. The NMDA agonist Riluzole is supposed to be better for depression, but is about $600 a month. And nothing I can find about MAOI effetcs. I am curious if anyone out there knows anything about memantine and MAO.
Posted by g_g_g_unit on October 16, 2009, at 5:51:00
In reply to Re: Memantine as a reversible MAO Inhibitor?, posted by Rosy Crucifiction on October 15, 2009, at 23:22:02
> Yes. I'm currently taking:
> memantine 15 mg. (start 20 next week)
> wellbutrin xl 300 mg (brand - generic sucks)
> concerta 72 mg (MUCH better than ritilin for me)
> liorix 150 mg (150 mg t4 / 30 mg t3)
> deplin
> test. cypionate
> I am MDD no psychosis, ADHD (inattentive), SAD and soft bipolar 2. The memantine has added real antidepressant effect and some hints of ability to experience pleasure. Titration has been tough for me. The first 3-4 days at 5 mg and at each 5 mg increase I have felt weak, strange, and like I couldn't handle the med. Within 4-5 days taht has changed to a real brightening of mood and a feeling of hopefulness. I now feel well enough to sign up for outpatient treatment at a depression center hospital (it's tough when you're too sick to deal with getting better). Anyway, the MAO bit is quite interesting. The NMDA agonist Riluzole is supposed to be better for depression, but is about $600 a month. And nothing I can find about MAOI effetcs. I am curious if anyone out there knows anything about memantine and MAO.i tried memantine as monotherapy. at 5mg it had a pleasant stimulating effect; the higher i went up the more anxiolytic it became, but i got really bad brain fog on it. the highest i went was 20mg.
i couldn't afford to take a really high dose (40mg a day or whatever) since i was taking the brand name, and medical insurance doesn't cover meds (especially off-label Alzheimers drugs) where i live.
anyway, once i began to taper off, there were a couple of days where i felt really good. i wonder if due to the long half-life i was taking too much for my individual case. i also wondered if maybe since the drug stabilizes the glutamate system, it might work better with another drug that's stimulating glutamate in some way. otherwise you just end up with the kind of middling depersonalization i experienced. that's my layman's theory anyway. i considered trying it with Wellbutrin at some point.
Posted by Rosy Crucifiction on October 16, 2009, at 11:22:02
In reply to Re: Memantine as a reversible MAO Inhibitor?, posted by g_g_g_unit on October 16, 2009, at 5:51:00
Memantine is clearly a weird drug. If I read the paper correctly, the authors say that taking 20 mg a day eventually leads to plasma concentrations high enough to lead to brain levels where MAO inhibition occurs. So it could be that negative reports have to do with a period where NMDA blockage led to uncomfortable side effects but MAO inhibition hadn't (yet?) occurred. So maybe it would have worked over a longer period of time.
How long where you at 20 mg? looking back do you think it could be too low a dose, too high a dose (you said you did well on 5mg) or ot long enough at 20mg. I'd appreciate a gut check, since I suspect I'm about to deal with the same sort of thing.
Posted by g_g_g_unit on October 16, 2009, at 20:00:47
In reply to Re: Memantine as a reversible MAO Inhibitor?, posted by Rosy Crucifiction on October 16, 2009, at 11:22:02
> Memantine is clearly a weird drug. If I read the paper correctly, the authors say that taking 20 mg a day eventually leads to plasma concentrations high enough to lead to brain levels where MAO inhibition occurs. So it could be that negative reports have to do with a period where NMDA blockage led to uncomfortable side effects but MAO inhibition hadn't (yet?) occurred. So maybe it would have worked over a longer period of time.
> How long where you at 20 mg? looking back do you think it could be too low a dose, too high a dose (you said you did well on 5mg) or ot long enough at 20mg. I'd appreciate a gut check, since I suspect I'm about to deal with the same sort of thing.i was only on 20mg for about two weeks. the effect was really inconsistent; there were days at 10/15mg where i felt incredibly placated and at peace, then others where i felt kinda down. 5mg was the best for social anxiety, but worsened my compulsions. i was just following the guideline which recommends 20mg .. i mean, i read about another girl who took 5mg twice a day to clear up brain fog while on mood stabilizers and that worked perfectly for her; she'd been on it for a year. it has some action on acetylcholine downregulation which i had read only lasts a week (hence the initial fuzziness) which is why i wasn't especially patient; but maybe the MAO effect warrants more time like you say.
unfortunately, like i mentioned the drug's a little too expensive to experiment with it. i might buy the generic online and try adding it to parnate or whatever i try next.
Posted by Rosy Crucifiction on October 16, 2009, at 22:43:07
In reply to Re: Memantine as a reversible MAO Inhibitor?, posted by g_g_g_unit on October 16, 2009, at 20:00:47
It sucks it's expensive in the states. FYI brand (Akatinol made by Merz) in Mexico is about $2.15 per 10mg.
Posted by g_g_g_unit on October 17, 2009, at 2:12:56
In reply to Re: Memantine as a reversible MAO Inhibitor?, posted by Rosy Crucifiction on October 16, 2009, at 22:43:07
i live outside the US. a box of thirty 10mg tablets (as Ebixa) cost me about $130US i think.
i've often thought a stimulant + memantine combination would be the best treatment for my symptoms. unfortunately, my (ex-)psychiatrist nearly had an aneurysm when i asked for methylphenidate (stims are heavily controlled here).
if you don't mind my asking - did you start Wellbutrin close to the Memantine? i have heard that there's a "honeymoon" period experienced on Wellbutrin with a great mood boost, etc. but that after that it just devolves into a generic stimulant without much potential for anhedonia. on a different forum one guy was questioning whether Memantine could be used to prevent tolerance to that "honeymoon" period in the same way it's used to prevent tolerance to other stims.
i was thinking it might be worth a shot. i have a Wellbutrin XR (brand-name) prescription i never used because i'm almost 100% the drug would cause anxiety in me in isolation. do you believe Memantine might also be helping control the anxiety from the stims you're on?
Posted by Rosy Crucifiction on October 17, 2009, at 11:14:55
In reply to Re: Memantine as a reversible MAO Inhibitor?, posted by g_g_g_unit on October 17, 2009, at 2:12:56
Yes, wellbutrin did seem to have a honeymoon period. I took 300 mg and then went to 450, even considered 600. But as maintenance therapy it noticeably effects norepinephrine. I'm less sleepy and have a bit more drive on it.
As to Docs and stims. The only way I have found to reliably get methylphenidate (or other stims, although I think methylphendiate is safer as just a DRI) is to discuss them in terms of adult ADHD. I have printed out an adult ADHD test. Here are links to two:
http://www.centerforpediatrics.com/index.php?option=com_content&task=view&id=53&Itemid=30
http://www.med.nyu.edu/psych/assets/adhdscreen18.pdf
What is interesting to me is the similarities in diagnostic criteria for adult adhd inattentive and bipolar 2. The only real difference I can see is that BP2 has a cyclical component (which, confusingly, may not manifest) and adhd diagnosis depends a lot on childhood symptoms.
Anyway, I've been able to walk in off the street in Mexico, and France and get a scrip for concerta. The fact that it has very low abuse potential compared to Ritilan helps. Anyway, good luck with it. Have you tried Emsam? I've found it quite helpful with the same symptoms.
Posted by g_g_g_unit on October 18, 2009, at 0:33:52
In reply to Re: Memantine as a reversible MAO Inhibitor?, posted by Rosy Crucifiction on October 17, 2009, at 11:14:55
Stims probably aren't the be-all-and-end-all i once imagined. i've tried Ritalin a couple of times, but the NE was too much; concerta is the primarmy stimulant used in my country.
i'd like to try something smoother like dexedrine, but i probably have more chance of winning the lottery than having that prescribed, not to mention that it would have to be imported.
EMSAM isn't available here either alas.
Posted by tropicalmanna on October 18, 2009, at 2:55:52
In reply to Memantine as a reversible MAO Inhibitor?, posted by Rosy Crucifiction on October 15, 2009, at 13:07:33
Thank you for the article!
In my experience high dose memantine works well as a fast acting antidepressant but is tricky to maintain because multiple high doses accumulate upon days to cause an unpleasant dissociative state. If anyone here is thinking about trying high dosing one must be aware that as a monotherapy it may make you experience OCD-like behavior and negative symptoms of schizophrenia. In addition, its 5HT antagonizing properties diminish the antidepressive response. Combined with a serotonin boosting med or a d2-antagonist one may be able to harness memantine's full potential for long-term use.
~TM
Posted by Rosy Crucifiction on October 18, 2009, at 13:06:33
In reply to Re: Memantine as a reversible MAO Inhibitor?, posted by tropicalmanna on October 18, 2009, at 2:55:52
I've wondered if the dissociative effects (mostly mental fog for me) are dose dependent or time dependent. Do they fade over time? Most people on the board who've discontinued memantine seem to have increased dosages over time until the side effects overwhelmed any advantage. Does anyone have experience with the side effect diminishing at a stable dosage (20mg is Merz's recommended dose)?
Posted by Rosy Crucifiction on October 18, 2009, at 13:20:43
In reply to Re: Memantine as a reversible MAO Inhibitor?, posted by Rosy Crucifiction on October 18, 2009, at 13:06:33
I added memantine to my concerta at onset hoping to ward off the tolerance I'd previously experienced with methylphenidate. The concerta form is new to me and has a very different effect form Ritilan. Long slow ramp to stimulation, so no euphoria or drug seeking. But it has eradicated my paralyzing fatigue.
More of a surprise to me is the combined effect on anhedoia. Doing a little reading, I found one study showing the tolerance preventing effect of mem. on methyl. in mice. Another showing memantine increases dopamine release in rat prefrontal cortex and striatum. Particularly D2, which seems to be related to the pleasure derived from drinking alcohol. And I've been drinking less. It's nice when there's a period of relief.see: NMDA receptor antagonist disrupts acute and chronic effects of methylphenidate.
Yang P, Swann A, Dafny N.Memantine-induced dopamine release in the prefrontal cortex and striatum of the rat--a pharmacokinetic microdialysis study.
Spanagel R, Eilbacher B, Wilke R.http://www.ionchannels.org/showabstract.php?pmid=18000814&redirect=yes&terms=d2+dopamine+memantine
Alcohol preference and sensitivity are markedly reduced in mice lacking dopamine D2 receptors
Tamara J. Phillips1, 2, 3, Kelly J. Brown3, Sue Burkhart-Kasch2, 3, Charlotte D. Wenger1, 2, 3, Michele A. Kelly4, 5, Marcelo Rubinstein7, David K. Grandy2, 5, 6 & Malcolm J. Low2, 4
Posted by g_g_g_unit on October 18, 2009, at 19:43:47
In reply to Re: Memantine as a reversible MAO Inhibitor?, posted by Rosy Crucifiction on October 18, 2009, at 13:06:33
> I've wondered if the dissociative effects (mostly mental fog for me) are dose dependent or time dependent. Do they fade over time? Most people on the board who've discontinued memantine seem to have increased dosages over time until the side effects overwhelmed any advantage. Does anyone have experience with the side effect diminishing at a stable dosage (20mg is Merz's recommended dose)?
you're right. if Memantine were to begin to inhibit MAO at a certain dose, then that might help with the dissociative effect. i only stayed on it for a couple of weeks; i don't know of anyone who really stuck with it long-term after the initial stimulation wore off
Posted by Rosy Crucifiction on October 18, 2009, at 20:35:08
In reply to Re: Memantine as a reversible MAO Inhibitor? » Rosy Crucifiction, posted by g_g_g_unit on October 18, 2009, at 19:43:47
I would agree. I've been wondering if the concerta / memantine synergy is helping to mitigate the memantine side effects.
Posted by linkadge on October 20, 2009, at 18:07:15
In reply to Re: Memantine as a reversible MAO Inhibitor?, posted by Rosy Crucifiction on October 18, 2009, at 20:35:08
Wow, it has some appreciable affinity for MAO and DAT. I'm suprised it doesn't have abuse potential. Ohter drugs like ketamine with NMDA and DAT affinity do.
Many NMDA antagonists (memantine, ketamine, zinc, DXM) seem to have some affinity for DAT. I am wondering if NMDA antagonism has some downstream effect on DAT).
Linkadge
Posted by Rosy Crucifiction on October 21, 2009, at 10:59:38
In reply to Re: Memantine as a reversible MAO Inhibitor?, posted by linkadge on October 20, 2009, at 18:07:15
There seems to be something going on between the concerta and memantine which supports DAT effects. I have never felt methylphenidate to have mood brightening effects other than short term euphoria with rapid release Ritilan. I have felt for a couple of weeks waves of the sort of positive affect I get from dopamine agonists. The agonists never last though.
Posted by g_g_g_unit on October 24, 2009, at 3:49:50
In reply to Re: Memantine as a reversible MAO Inhibitor?, posted by Rosy Crucifiction on October 21, 2009, at 10:59:38
i heard that Memantine was able to prolong the mood-boost from stimulants (not just Wellbutrin, as i mentioned earlier, but concerta, etc. as well) by preventing tolerance. do you feel more of a general anti-depressant effect from the concerta, or do you still require the wellbutrin as an AD?
Posted by Rosy Crucifiction on October 24, 2009, at 12:26:45
In reply to Re: Memantine as a reversible MAO Inhibitor?, posted by g_g_g_unit on October 24, 2009, at 3:49:50
I definitely need the wellbutrin. I start to get a pressor effect from the increased Norepinephrine at 300 mg. I've been playing around with bp meds to see what doesn't throw mood off track. Lisinopril seems to work and gets BP back to 120/70. I might benefit from 450 on the Wellbutrin, but I don't like having to try to offset a major BP increase.
FYI - dissociative effects. 20 mg for a week and I started to feel bad - weird. So I'm going back to 15 to see if that was the issue. It has an 80 hour half life but T-max is about 6 1/2 hours. So who knows. I'll post again when I feel like I've resolved this.
BTW - have you had any experience with Valdoxan (agomelatine)? How was parnate?
Posted by g_g_g_unit on October 24, 2009, at 23:56:17
In reply to Re: Memantine as a reversible MAO Inhibitor?, posted by Rosy Crucifiction on October 24, 2009, at 12:26:45
no. i hear valdoxen has a similar mechanism to remeron, which was hell for my OCD. as anti-depressants, the MAOI's are unparalleled in my opinion, but i cannot deal with the Parnate insomnia, and have started to taper off; if i treat it seroquel it kills the AD effect, but if i stake awake i feel like i'm going crazy. last week i slept like 2 hours each night.
i am actually convinced i have ADHD, which is where my OCD (perfectionism) stems from - as a kidn of coping mechanism. docs have been happy to throw every zombifying silver bullet at the OCD (antipsychotics, anafranil), but nothing seems to help my executive dysfunction. i've applied for ADHD testing, because stims are completely restricted otherwise.
my hope was in trying something like concerta (the primary stim here unfortunately) + memantine, as this seems to be a life-changing combo for many with both afflictions.
Posted by g_g_g_unit on October 25, 2009, at 0:21:17
In reply to Memantine as a reversible MAO Inhibitor?, posted by Rosy Crucifiction on October 15, 2009, at 13:07:33
reading over your first post again .. "Memantine at 1mM inhibited both MAO-A and MAO-B activities in mouse forebrain homogenates to 37% and 64% of controls, respectively. "
5-HT and dopamine reuptakes were inhibited to 2% and 16% of controls, respectively, with 1mMmemantine. "
i mean, what do those figures mean anyway? is 37% and 64% MAO-A and B inhbition a significant amount, etc.? how would they compare to standard irreversible MAOI's?
Posted by Rosy Crucifiction on October 25, 2009, at 10:04:23
In reply to Re: Memantine as a reversible MAO Inhibitor?, posted by g_g_g_unit on October 25, 2009, at 0:21:17
Regarding percentages, great point. I just did a search on Parnate and MAOIs to try to find out and got nothing. I'll dig a bit more. Maybe too much inhibition is why MAOIs can be tough o tolerate.
You seem down on Concerta. I've tried Adderall XL, Ritilan SR and Concerta.I MUCH prefer Concerta.The other two initailly caused euphoria. Which was great, but cr*pp*d out quickly and left me feeling bad. Plus I felt like I was doing recreational drugs the whole time. I was always acutely aware of their effect and tended to try to manage it (should I take more?). The Concerta is just a pill I take in the morning. I set my alarm for 2 hours before I want to get up and take it, the Wellbutrin, Deplin, 1/2 the memantine and Liotrix. By the time I want to get up (on a good day) I feel ready and reasonably together.
The dopamine and norepinephrine enhancement of the thyroid, and the ADs is a real help.
As I said, I dropped back down the memantine and feel better. I'm adding sertraline 50 mg and pindolol 7.5 mg in the evenings for BP and possible acceleration of AD effect.
BTW - if you haven't tried tweaking thyroid, I recommend it. I got a lot of antidepressant effect, better focus, motivation and improved energy from it. My thyroid was normal. I'm on the equivalent of 150 mcg t4 and 30 mcg t3. I've tried higher doses with better mood effect, but got some arrhythmia. It's cheap and easy to get. Keep me posted on how the ADHD stuff goes.
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