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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 8 of 8. This is the beginning of the thread.
Posted by JohnX on March 14, 2001, at 2:24:04
Wondering if there are any clean, directed,
and potent alpha-1 adrenergic agonists that may
be useful adjuncts to meds like serzone or zyprexa
which partially antogonize alpha-1 receptors (making
us fat and dizzy) ?Modafinil is rumored to be an alpha-1 agonist,
but the manufacturer's PDF claims that the mode
of action is unknown.-John
Posted by JohnL on March 14, 2001, at 4:34:30
In reply to Any potent Alpha-1 adrenergic agonists? , posted by JohnX on March 14, 2001, at 2:24:04
>
> Wondering if there are any clean, directed,
> and potent alpha-1 adrenergic agonists that may
> be useful adjuncts to meds like serzone or zyprexa
> which partially antogonize alpha-1 receptors (making
> us fat and dizzy) ?
> -JohnHi John,
You just described Adrafinil. I can say from my own personal experience that it is awesome when combined with SSRIs and/or antipsychotics. It not only acts as a synergistic turbocharger with other meds, but it also counteracts alpha-1 antagonism. It is a direct alpha-1 adrenergic agonist. There were posts here a few months ago that stated that the inventor of Adrafinil claimed that it was NOT an alpha-1 agonist. Despite that, the manufacturer and the label and everything I can find in literature state that it is. It's primary action is as an alpha-1 agonist, and there is clinical evidence suggesting that it also enhances D2 dopamine function. Both of those mechanisms are highly useful in treating depression.Another option could be Nicergoline, though I've never heard of anyone using it. I ordered some a few months ago but never tried it. It gathers dust in a storage box. I can tell you from personal experience though that Adrafinil fits the description of what you are looking for.
John
Posted by AndrewB on March 14, 2001, at 10:11:18
In reply to Re: Any potent Alpha-1 adrenergic agonists? , posted by JohnL on March 14, 2001, at 4:34:30
John,
Too much alpha 1 receptor agonisim can be problematic, having numerous possible side effects including sexual dysfunction, urinary hesitancy, anxiety, and (often) eventual poop-out.
That being said, I believe phenlyephrine is a fairly selective alpha 1 agonist. I know nothing more about it though.
Adrafinil (and possibly Provigil) may be a centrally acting alpha 1 agonists. Thereby giving the arousal effects of alpha 1 agonism without the periphereal side effects.
Stimulants stimulate the andrengic system in general.
Trycyclics which have a strong NE action component are often successfuly combined with serotenergic agents.
Reboxetine, as an NE reuptake inhibitor, has been used as an arousal agent though it can cause all (and then some) of the side effects listed above. People have found that serotenergic agents when combined with reboxetine can eliminate the anxiety or jumpy feeling that it may cause.
Those who quickly want to see if they will benefit from alpha 1 agonism can try Naphazoline eye drops. Bought over the drugstore counter, it acts within 10 or so minutes (it also has a short half-life). A person who responds to it, that is gets a positive arousL effect, may well benefit from the longer acting drugs described above.
Naphazoline is sold under a variety of tradenames like Vasocon and Naphcon. Look at the active ingrediants on the bottle. It should list .01% Naphazoline Hydrochloride as its active ingrediant. Do not buy eyedrops that contain other active ingrediants. For example, brands that have an 'A' at the end of their name (i.e. VasoconA), contain an antihistamine also as an active ingrediant.
Naphazoline is not recommended for long-term use. It tends to poop out after repeated dosing. Some people though have used it for over 3 years for arousal effects.
Excessive naphazoline can increase blood pressure, pulse rate, and sweating, and it can cause agitation, anxiety and insomnia.
Apply the eyedrops by first washing your hands (also keep the eyedrop bottle applicator clean and germ free). Then, tilt your head back and apply pressure with the middle finger to the inside corner of the eye (the tear duct). Apply one or two eyedrops per eye and continue the finger pressure for 1 or 2 minutes afterwards.
Insert the eyedrops by pulling down the lower eyelid with the middle finger to create a pouch. Drop in the eydrops, close your eyes and keep them shut and don't blink for one or two minutes. If after ten or so minutes you do not feel anything, repeat the dosing one more two times.
AndrewB
Posted by PhoenixGirl on March 14, 2001, at 17:08:04
In reply to Any potent Alpha-1 adrenergic agonists? , posted by JohnX on March 14, 2001, at 2:24:04
Is it physical or is it libido-related? I thought that alpha-1 adrenergic agonists would improve sexual function if anything. Maybe I have it backwards, i don't know. What does Flomax do?
>
> Wondering if there are any clean, directed,
> and potent alpha-1 adrenergic agonists that may
> be useful adjuncts to meds like serzone or zyprexa
> which partially antogonize alpha-1 receptors (making
> us fat and dizzy) ?
>
> Modafinil is rumored to be an alpha-1 agonist,
> but the manufacturer's PDF claims that the mode
> of action is unknown.
>
> -John
Posted by SLS on March 15, 2001, at 6:11:26
In reply to Re: Any potent Alpha-1 adrenergic agonists? , posted by AndrewB on March 14, 2001, at 10:11:18
> That being said, I believe phenlyephrine is a fairly selective alpha 1 agonist. I know nothing more about it though.
I think the problem with phenylphrine is that it does not cross the blood-brain barrier.
- Scott
Posted by AndrewB on March 15, 2001, at 10:36:44
In reply to What sexual side effects do they cause?, posted by PhoenixGirl on March 14, 2001, at 17:08:04
Sexual side effects are physical and I believe only effect men. Specifically it causes a tightening of certain (smooth?) muscles surrounding the urinary canal and, apparently, the groin region in general. Alpha 1 agonism can result in difficulty in achieving erection and retorgrade ejaculation. Flomax is an alpha 1 receptor blocker used for enlarged prostate conditions but also has been used in combo with reboxetine (an NE reuptake inhibitor) to eliminate the sexual and urinary difficulties that reboxetinbe can cause. As I said, I think these sexual (an urinary?) problems are limited to men.
AndrewB
Posted by JohnX on March 16, 2001, at 0:05:29
In reply to Re: What sexual side effects?: Phoenix Girl, posted by AndrewB on March 15, 2001, at 10:36:44
> Sexual side effects are physical and I believe only effect men. Specifically it causes a tightening of certain (smooth?) muscles surrounding the urinary canal and, apparently, the groin region in general. Alpha 1 agonism can result in difficulty in achieving erection and retorgrade ejaculation. Flomax is an alpha 1 receptor blocker used for enlarged prostate conditions but also has been used in combo with reboxetine (an NE reuptake inhibitor) to eliminate the sexual and urinary difficulties that reboxetinbe can cause. As I said, I think these sexual (an urinary?) problems are limited to men.
>
> AndrewB
Ok, my original thought was what medication could be combined with the a1 partial antagonists to offset the side-effects caused by a1 antagonism?
A lot of people complain about the side effects
of Serzone/Zyprexa et. al who are sensitive to the weight gain or dizziness and so it just seems like dosing in a countermeasure to go straight after the problem is worthwhile.Here is my summary of a1 antagonism side effects:
-priapiam (particularly in Trazodone, the older Serzone)
-dizziness
-drowsiness
-weight gain
-low blood pressure (postural hypotension)Here are the a1 agonist side effects
-urinary retention
-impotence
-excitability
-weight loss
-possible improvement in cognitionI'm always willing to take two meds even if I can't stand them by themselves, but their side effects cancel out. Seems to have worked for me
in the past if you get the dosing ratio of the
two meds correct.That being the case, it seems like dosing in some amount of the meds adrafinil/reboxetine/etc may
be extremely useful to me if I want to try
Serzone again (which was overwhelmingly drowsy and
dizzy after a long trial), or an anti-psychotic with similar properties like Zyprexa. Geodon does not have the alpha-1 antagonism to the same extent and as such would be less likely to cause the problems.I have read about the Flomax trick adding it to Reboxetine. This is just the same idea in reverse. Always wondered if anyone tried a Serzone/Reboxetine combo (to combat the impotence and urinary retention)?
Also, back to my original post. Do you guys know if Modafinil (Provigil) is an A1 agonist? I have a script for this (expensive!, insurance whines)and tried it for 3 days as a substitute for Adderall. It made me less irritated, but gave me a big headache as if I drank 8 pots of coffee and had little impact on my mood (although it did help with concentration).
Thanks for all your feedback.
I'm on page with AndrewB who a long time ago
told me that he's a big fan of "clean" meds.
My take is that if we've gone through the ringer
and have found a med(s) that address a large portion of our difficulties with just 1 or 2 unbearable side-effects, then dosing in a clean-med that directly counteracts the well-known biological reason for the side-effect is a good idea.-John
Posted by AndrewB on March 16, 2001, at 9:45:17
In reply to Re: Any potent Alpha-1 adrenergic agonist, posted by JohnX on March 16, 2001, at 0:05:29
John,
I have a lot of unresolved questions about NE drugs in general, specifically when and how they provide efficacy.
I do not know of anyone using an alpha agonist to counteract the properties of another drug’s alpha 1 antagonism.
Direct acting agents of alpha 1 agonism include: phenylethamines, phenylephrine, methoxamine, metraminol, imidazolines, oxymetazoline, tetrahydrozoline and naphazoline.
I don't know anything about the actual effects of the drugs on the above list except naphazoline. As I mentioned in an above post, naphazoline, though not necessarily a permanent solution, will give you a quick idea of whether alpha 1 agonism will help you counter the effects of alpha 1 antagonism.
Adrafinil and Provigil both gave me headaches and made 'tense'. Comparing the effects of these meds to reboxetine and naphazoline, I felt that Provigil and adrafinil, if they do have alpha 1 agonist action, the action is centrally acting and thus will not counteract the peripheral effects of alpha 1 antagonism. Both these meds also reportedly have glutaminegic action (i.e. increasing glutaminergic activity in the hippocampus.) This may the actual mode of action for these drugs.
First hand reports on reboxetine seems to indicate that it rarely provides mood benefit as a stand alone, while, interestingly, inducing depression in a select number of people. It is not what I would consider a clean drug. It seems to have a broad action which induces a variety of side effects in various people.
There is the idea that people with treatment resistant depression will benefit from a combo of reboxetine + an SSRI inhibitor. Caution is warranted though. Serzone is marked inhibitor of the liver enzyme CYP3A4. Reboxetine is primarily metabolized by this enzyme. The combo may lead to increased reboxetine blood levels and side effects.
Sunnely in a post suggested that among the SSRIs, citalopram (Celexa), is probably the top choice to combine with reboxetine for people with treatment resistant depression. Celexa has little or no effect on the CYP3A4 enzyme, therefore it isn’t likely to have a pharmokinetic interaction with reboxetine. Also celexa is, according to Sunnely, the most selective SSRI., while rebox. is selective for NE. So apparently there is not an overlap in their actions. There is a published report of 4 treatment resistant patients benefiting from this combo.
AndrewB
This is the end of the thread.
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