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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 5 to 29 of 29. Go back in thread:
Posted by university on October 30, 2005, at 21:21:20
In reply to Re: DPSP database clomipramine dopamine affinity, posted by iforgotmypassword on October 30, 2005, at 20:51:42
i'm not sure--i was just responding to zeugma's post.
the only antidepressant i know of that can cause td is "Asendin" (amoxepine).
Posted by zeugma on October 30, 2005, at 22:28:01
In reply to Re: DPSP database clomipramine dopamine affinity, posted by iforgotmypassword on October 30, 2005, at 20:51:42
> are the tricyclics so directly descended from the early antipsychotics this? any other tricyclics with wierd surprises?>>
the tricyclics are all directly descended from the phenothiazines. In fact imipramine, amitriptyline, and clomipramine were all developed for neuroleptic potential; it was a major disappointment that they failed to work as neuroleptics. In the course of these trials an antidepressant effect was discerned, which was unexpected (although neuroleptics themselves may/may not have antidepressant effects; certainly unlike the TCA's this is not their most striking effect).
university is correct that ascendin has major potential to cause TD. But it is a cross pharmacologically between the TCA's and phenothiazines, not necessarily structurally (it has a close resemblance to loxapine). Clomipramine has been around for many years (though not in the U.S.), and i don't think it's considered a significant risk for TD. The hazard to watch out for is serotonin syndrome, when combined with an SSRI or especially a MAOI (this last is a strict contraindication).
the tricyclics are an especially well-studied group of drugs. i don't think weird surprises are a problem with them, although many do have considerable s/e.
clomipramine is chlorinated imipramine. If you add a sulfur atom to CMI's central ring, you have chlorpromazine.
the TCA's do have many resemblances to the early AP's, but some of these (e.g. antagonism of the 5ht 2 receptors) are considered potential antidepressant mechanisms.
-z
Posted by med_empowered on October 30, 2005, at 22:37:03
In reply to Re: DPSP database clomipramine dopamine affinity, posted by zeugma on October 30, 2005, at 22:28:01
hey! I think I've read that extended, high-dose clomimpramine use can sometimes lead to some form of TD...I guess this would be kind of like the cases of TD that pop up now and then with Effexor, and more commonly with amoxapine. Surmontil also has an odd, neuroleptic-ish effect; chemically, its a lot like loxapine...apparently, the D2 antagonism is really, really mild, so you don't see EPS, and I don't think there have been any problems with TD. The good news is that it can kind of function as a mood-stabilizer and antidepressant at usual doses, which makes it ideal for people with bipolar or more complicated cases of unipolar depression. I think I read a study where it was used for schizophrenia, but I dont think the results were all that promising.
Posted by linkadge on October 31, 2005, at 9:12:24
In reply to clomimpramnie, td, posted by med_empowered on October 30, 2005, at 22:37:03
The clomipramine kind of felt like taking an SSRI and and zyprexa.
The anticholinergic effects may have masked any EPS I was experiencing.
The d2 blockade may also have additional anti-OCD efficacy since sometimes d2 antagonists are used as adjunctive to refractory OCD.
Linkadge
Posted by Larry Hoover on October 31, 2005, at 12:59:45
In reply to DPSP database clomipramine dopamine affinity, posted by linkadge on October 30, 2005, at 19:29:39
> I was searching the affinitiy of clompipramine for dopamine receptors in the PDSP database.
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> It seemed to have a fairly strong afinity for the d2 receptor (Ki 77). I cannot discriminate from the site weather this is an agonist or antagonist value.That's the biggest drawback of this database; it doesn't indicate agonism/antagonism. The hotlinks in the right column, that take you to the Pubmed abstract, sometimes give you the answer. Other times, I've been able to find out by doing Google searches using the receptor subtype as one of the keywords.
Lar
Posted by Tom Twilight on October 31, 2005, at 13:51:30
In reply to Re: DPSP database clomipramine dopamine affinity » linkadge, posted by Larry Hoover on October 31, 2005, at 12:59:45
judging from my experience of Clomipramine I would have thought it was a D2 antagonist
It was very effect for anxiety, although not social anxiety, it was also very sedating and somewhat dulling.
That doesn't seem consistant with what I know about D2 stimulation!
Posted by ed_uk on October 31, 2005, at 15:07:36
In reply to Re: DPSP database clomipramine dopamine affinity, posted by University on October 30, 2005, at 20:13:23
Hi J,
>So clomipramine is essentially an antipsychotic?
No. It's a weak D2 antagonist. It's a potent reuptake inhibitor: it acts as an antidepressant.
Kind regards
Ed
Posted by rod on October 31, 2005, at 18:09:51
In reply to Re: DPSP database clomipramine dopamine affinity » University, posted by ed_uk on October 31, 2005, at 15:07:36
Clomi is gooooood, mkay ? ;-)
And its no way like the numbdumb feeling Zyprexa gives *me* (2,5mg)... Even Amisulpride was dulling the first few days. But, well, anyone is different.. your mileage may vary, I guess..... Anyway. Knowledge about its receptor affinities should not be a reason not to try this very efficient antidepressant IMO...bye bye
Roland
Posted by linkadge on October 31, 2005, at 18:21:49
In reply to Re: DPSP database clomipramine dopamine affinity, posted by rod on October 31, 2005, at 18:09:51
I know what you are saying. Recepor affinities may be a reason to watch for potential problems such as TD. There have been case reports of TD with high dose clomipramine.
Linkadge
Posted by blueberry on November 1, 2005, at 8:11:44
In reply to DPSP database clomipramine dopamine affinity, posted by linkadge on October 30, 2005, at 19:29:39
Desipramine also has affinity for dopamine D2 receptors. Probably antagonism (guess), but no idea if at presynaptic or postsynaptic or both.
Just a guess, but I would bet all of the TCAs interact with dopamine receptors in one way or another.
Posted by ed_uk on November 1, 2005, at 15:49:52
In reply to Re: DPSP database clomipramine dopamine affinity, posted by rod on October 31, 2005, at 18:09:51
Hi Roli,
Despite the side effects, clomipramine does have the advantage that it works :-)
Ed
Posted by linkadge on November 1, 2005, at 17:28:35
In reply to Re: DPSP database clomipramine dopamine affinity » rod, posted by ed_uk on November 1, 2005, at 15:49:52
One of the reasons that clomipramine is so effective (in my bitter opinion :) ) is that it is a high octane dumb drug.
Linkadge
Posted by zeugma on November 1, 2005, at 18:37:42
In reply to Re: DPSP database clomipramine dopamine affinity, posted by linkadge on November 1, 2005, at 17:28:35
> One of the reasons that clomipramine is so effective (in my bitter opinion :) ) is that it is a high octane dumb drug.>>
Maybe you'd like a low octane dumb drug, like nortriptyline, better :)
-z
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Posted by zeugma on November 1, 2005, at 19:47:29
In reply to Re: DPSP database clomipramine dopamine affinity, posted by linkadge on November 1, 2005, at 17:28:35
> One of the reasons that clomipramine is so effective (in my bitter opinion :) ) is that it is a high octane dumb drug.>>
anticholinergic effects can impair memory, but I seriously, seriously doubt that memory impairment is the mechanism by which they may contribute to alleviation of depressive states.
Klonopin can cause serious memory impairment, and yet it has a reputation for causing depression. And drugs that enhance memory, such as anti-Alzheimer's drugs, whose pro-cholinergic effect is the opposite of clomipramine's, are notably ineffective in treating depression, and appear to be even more depressant than Klonopin.
-z
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Posted by linkadge on November 1, 2005, at 21:28:09
In reply to Re: DPSP database clomipramine dopamine affinity » linkadge, posted by zeugma on November 1, 2005, at 19:47:29
>anticholinergic effects can impair memory, but I >seriously, seriously doubt that memory >impairment is the mechanism by which they may >contribute to alleviation of depressive states.
THe TCA's are arguably more effective for certain depressive states than newer drugs, even say, effexor, which shares the TCA's dual uptake inhibiting properties. The main difference are the anticholinergic side effects. Anticholinergics are oftentimes euphoriants. I personally find anticholinergics very mood brightening. I found cogentin was an antidepressant.
I personally do not doubt that impairment of certain aspects of memory can have antidepressant effects, so as to agree with Breggin's theory of "Brain Disabling Treatments", essentially where many "theraputic responses" in psychiatry correspond directly to impairment of some aspect of neurological functioning. What do ECT and TCA's have in common besides their higher efficacy in depression? Memory impairment, among other dirty consequences.
Linkadge
Posted by zeugma on November 1, 2005, at 21:49:27
In reply to Re: DPSP database clomipramine dopamine affinity, posted by linkadge on November 1, 2005, at 21:28:09
> >anticholinergic effects can impair memory, but I >seriously, seriously doubt that memory >impairment is the mechanism by which they may >contribute to alleviation of depressive states.
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> THe TCA's are arguably more effective for certain depressive states than newer drugs, even say, effexor, which shares the TCA's dual uptake inhibiting properties. The main difference are the anticholinergic side effects. Anticholinergics are oftentimes euphoriants. I personally find anticholinergics very mood brightening. I found cogentin was an antidepressant.
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> I personally do not doubt that impairment of certain aspects of memory can have antidepressant effects, so as to agree with Breggin's theory of "Brain Disabling Treatments", essentially where many "theraputic responses" in psychiatry correspond directly to impairment of some aspect of neurological functioning. What do ECT and TCA's have in common besides their higher efficacy in depression? Memory impairment, among other dirty consequences.>>why then is not Klonopin not an antidepressant? It causes cognitive impairments yet depresses people.
what about many AED's? people often complain that they impair memory but are not antidepressants.
Neurontin has been called "Morontin" by many posters and yet it has not been hailed as an antidepressant.
what was that notorious drug that was implicated in date rapes? Rohypnol? Shouldn't that by Breggin's logic be the ultimate antidepressant?
what I was trying to say in my previous post to you, but did not express clearly enough, no doubt beause i am on therapeutic doses of two 'dumb drugs' (clonazepam and nortriptyline) is that anticholinergic effects are antidepressant but that the effect is independent of cognitive disabling, because benzos cause arguably even greater cognitive impairment than TCA's and yet are not antidepressants.
-z
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Posted by linkadge on November 2, 2005, at 9:09:17
In reply to Re: DPSP database clomipramine dopamine affinity » linkadge, posted by zeugma on November 1, 2005, at 21:49:27
Like I said, not all dumb drugs are antidepressants, but the best antidepressants are dumb drugs.
The cognitive effects of the other drugs you mentioned are secondary to their anticonvulsant side effects.I think that if you ordered the antidepressants from least cognitively impairing to most, you would find that you have simultainiously ordered them from least to most clinically effective.
Linkadge
Posted by linkadge on November 2, 2005, at 9:11:43
In reply to Re: DPSP database clomipramine dopamine affinity » linkadge, posted by zeugma on November 1, 2005, at 21:49:27
Reality depresses me, therefore the best antidepressants for me are the ones that make me forget about reality, ie. the dumb drugs.
Linkadge
Posted by rod on November 3, 2005, at 7:34:08
In reply to Re: DPSP database clomipramine dopamine affinity, posted by linkadge on November 2, 2005, at 9:11:43
I are baboon :))
I are many much smart for world :))
So have increased from 75mg to 100mg. to be gaga :))
(thats pure self irony, and isnt related to other persons wheter on this board or in real life.)
nah, to be honest. I guess to a certain extend you are right. But this surely doesnt apply to all depressed persons.
And this actually this reminds me of a severely depressed (the crying type..) woman I met in hospital. She was on Remeron (60mg), Effexor (300mg) and Lexapro (40mg) and recieved ECT too... She didnt respond at all to the treatment. But after some days I found out she had problems with her marriage and so on. severe problems... Oh well, I highly doubt ECT or drugs will solve her marriage probelms... hmmmm
I "escaped" from there, so I do not know how things have turned out for her.anyway..... :) I are better memory when on dump druxs :))
bye
Roland
Posted by linkadge on November 3, 2005, at 14:27:24
In reply to Re: DPSP database clomipramine dopamine affinity, posted by rod on November 3, 2005, at 7:34:08
Wow!. I think there is a need for doctors to realize that sometimes less medication can actually make somebody better.
For instance, someone might be apathetic on 20mg of prozac. This could be interpreted as depression, and result in higher and higer doses of prozac. Then the doctor gives this person ECT, when all they really needed was less prozac.
Sometimes the drugs can make you sick.
Linkadge
Posted by ed_uk on November 3, 2005, at 16:57:30
In reply to Re: DPSP database clomipramine dopamine affinity, posted by rod on November 3, 2005, at 7:34:08
LOL Roli, are you gaga?
Ed!
Posted by zeugma on November 3, 2005, at 18:31:57
In reply to Re: DPSP database clomipramine dopamine affinity » rod, posted by ed_uk on November 3, 2005, at 16:57:30
> LOL Roli, are you gaga?
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> Ed!Hi Ed,
Online diagnosis is a tricky thing, but I suspect Roland of liking his TCA's a little too much. Consider this strange report:
Przegl Lek. 2005;62(6):397-8.
Recreational amitriptyline abuse.Sein Anand J, Chodorowski Z, Habrat B.
1st Clinic of Internal Diseases and Acute Poisonings, Medical University of Gdansk, Poland. jsanand@amedec.amg.gda.pl
Amitriptyline is a potent anticholinergics, rarely used as a drug of abuse. Two cases of amitriptyline dependency lasting for almost twelve months were described. According to the patients the abuse with amitriptyline guarantee them safety not to be uncovered by parents and doctors who systematically checked their urine with typical narcotic tests. CASE REPORT: Two patients with a history of abuse with amphetamine and clonazepam were admitted to the Clinic because of intoxication with amitriptyline. They denied the suicidal attempt and explained that they used amitriptyline in a dosage of 100 to 200 mg per day as a drug of abuse. On the day of admission one of the patients had increased the dosage up to 600 mg which caused an acute intoxication. CONCLUSION: Antidepressants should be treated as a drugs with possible abuse ability.>>
I wonder if the writers of this article were amitriptyline abusers themselves.
:-)
-z
Posted by linkadge on November 3, 2005, at 21:39:52
In reply to Re: DPSP database clomipramine dopamine affinity, posted by zeugma on November 3, 2005, at 18:31:57
It's really strange. I've taken a lot of antidepressants. Certain of which I would increase given the option, dispite the absence of depressive symptoms.
The first dose of clomipramine I took, was pleasureable. For about an hour after each dose, I would experience a host of pleasurable sensations.
Linkadge
Posted by rod on November 4, 2005, at 7:02:27
In reply to Re: DPSP database clomipramine dopamine affinity, posted by zeugma on November 3, 2005, at 18:31:57
> > LOL Roli, are you gaga?
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> > Ed!
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> Hi Ed,
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> Online diagnosis is a tricky thing, but I suspect Roland of liking his TCA's a little too much. Consider this strange report: ........hmm
well, actually all you can see is that i have a very childish/silly kind of humor. Thats just me...
And all this "I are .." stuff comes from a caartoon called "baboon and weasel" http://en.wikipedia.org/wiki/I_Am_Weasel (yes I still watch such stuff at my age from time to time ;)The day I did above post, I went to get a refill and surprisingly noticed that my facial sweating and flushing didnt happen when I talked to the nurse and at the pharmacy. And even when the nurse asked me to spell my name, I often cant think straight and have a hard time to spell my own name, because of my "social anxiety". I was just happy about this improvement and when I got home I did that post.
Guess its just a sign of reduced social anxiety, that I did such a post. just tried to be funny. "Normally" I am way to shy to post such things, because I fear that someoone does not like "my way" and rejects me and son on....I just didnt care about what some people might think about me, this time. its just me.
But I can understand that some people might think I like my drugs "too much"... but uh, all my friends noticed so far is described in statements like: How do you do? It seems you are doing better than last months? could it be?
So no wories. I am not running naked and screaming through the streets, by now :Panyway ... hrhr :)
bye
Roland
Posted by zeugma on November 4, 2005, at 20:16:18
In reply to Re: DPSP database clomipramine dopamine affinity » zeugma, posted by rod on November 4, 2005, at 7:02:27
roli, you and i are on the dumbest drugs imaginable
and yet we both have the wit to joke
:-)
-z
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