acetylcholine and libido?

Discussion in 'Men's Health Forum' started by chap, Jan 22, 2006.

  1. #1
    chap

    chap Junior Member

    searched here and came up with nothing, can anyone elaborate on the connection? would DMAE supplementation be a possible help for libido? or lecithin?
     
  2. #2
    marianco

    marianco Doctor of Medicine

    Perhaps, I should have corrected/clarified myself on an earlier posting.

    From Stephen Stahl's Essential Psychopharmacology textbook, there are three stages of the sexual response:
    1. Libido - involving a desire for sex or sex drive
    2. Arousal (erection, lubrication, swelling) - involving signaling the sex organs into action.
    3. Orgasm/ejactulation

    From what I know so far:

    Libido is increased by increased dopamine levels in the mesolimbic dopamine reward centers of the brain (note the specificity of localization). Increases in other areas may or may not negatively affect libido. Libido is decreased by increased prolactin levels - though dopamine itself reduces prolactin levels. Serotonin in the brain may reduce libido, by reducing dopamine levels among other effects. However, when anxious or stressed, a small increase in serotonin may help libido by reducing the perception of stress and by reducing anxiety (thus the usefulness of serotonin reuptake inhibitors in premature ejaculation). Acetylcholine (via interneurons) reduces dopamine release from dopaminergic neurons, and thus may reduce libido. Blocking NMDA glutamate receptors may increase dopamine levels. Increase norepinephrine levels (another stimulant neurotransmitter) may increase libido in some people, though excessive norepinephrine may reduce libido (since norepinephrine is a signal for stress). GABA is involved with libido. Increased GABA levels may reduce anxiety/stress, leading to increased libido. Excessively high GABA activity sedates - reducing libido. Increased histamine levels may potentially improve libido (Histamine is a stimulant neurotransmitter like dopamine and norepinephrine). However excessive histamine may trigger anxiety, anger, irritability, agitation, insomnia, and stress - reducing libido.

    Arousal involves transforming the sex drive into a signal from the brain to activate the genitals. Acetylcholine is involved in transmitting the signal through the parasympathetic nerves to the genitals. Nitric oxide (formed from L-arginine by Nitric Oxide Synthetase in nerves) is then released, activates the intracellular enzyme guanylyl cyclase, which then makes cyclic guanylate monophoasphate (cGMP), which relaxes vascular smooth muscle, opens blood flow, and causes and erection. cGMP's actions are terminated by Phosphodiesterase

    Orgasm/ejaculation involves norepinephrine, which transmits signals through the sympathetic nervous system to the genitals, to trigger orgasm and ejaculation. Serotonin signals from the brain through the spine, to the genitals inhibit orgasm.

    Blocking phosphodiesterase using viagra helps maintain blood flow into the penis, maintaining an erection.

    Prostaglandin E1 (Caverject), via injection to the penis, can relax vascular smooth muscle like nitric oxide, and can thus be used to obtain an erection, even if the nervous system is not signaling properly (e.g. impaired transmission due to diabetes).

    Wellbutrin in some people may improve libido by increasing norepinephrine level in the brain - depending on the dose. In my experience, high doses can impair libido - possibly by activating the adrenal glands (since norepinephrine is the signal for stress from the brain to the adrenals), causing an increase in cortisol, which causes transient insulin resistance, which reduces testosterone production, which then reduces dopamine levels.
     
    Last edited: Jan 22, 2006
  3. #3
    Matt Muscle

    Matt Muscle Junior Member

    Your answers are always so good to read... thankyou!
     
  4. #4
    chap

    chap Junior Member

    so would wellbutrin be a sure thing for those on trt, as the testosterone reducing effect would not be an issue, so we would only be left with the good libido effects?
     
  5. #5
    marianco

    marianco Doctor of Medicine

    Wellbutrin is not a sure thing. The effect of Wellbutrin depends on the dose. A low dose, in the absence of other complicating factors, may increase libido. A high dose may reduce libido. If I want to increase libido in a person, I usually will start at around 25 to 37.5 mg a day of Wellbutrin - regular release, not the extended release versions - and gradually increase the dose to a maximum of 150 mg a day. Past that dose, I haven't seen Wellbutrin work to improve libido. For example, one of my elderly female patients developed frequent spontaneous orgasms at 37.5 mg a day of Wellbutrin which disappeared at the higher dose needed to treat depression. If a person is stressed to begin with, their norepinephrine levels are already high. Even a low dose of Wellbutrin may not help in that case.

    Wellbutrin works by increasing norepinephrine activity in the brain - acting as a stimulant, improving concentrating, energy level, promoting wakefulness, etc. The problem is that norepineprhine is also a signal used by the brain to trigger the stress response.

    From what I know so far, in the stress response, high norepinephrine levels in the brain shuts down pleasurable responses in preparation to handle stress. This may occur by triggering anxiety, fear, anger - negative emotions. Norepinephrine also travels through the sympathetic nervous system, triggers activity in the adrenal glands. The adrenal glands start producing and releasing hormones to handle stress. The primary hormone released is cortisol. Cortisol causes immediate insulin-resistance in cells. This insulin-resistance reduces testosterone production, resulting in a reduction in libido - particularly if testosterone level is not at the high end of normal. The stress response is extremely quick - as it needs to be.

    Imagine a man making love with a woman in a hotel room in the morning. Suppose they forgot to put the "do not disturb" sign on the door. The maid attempts to open the door and enter the room. The man hears the door opening. He immediately becomes stressed. He quickly loses his erection.
     
  6. #6
    T Man

    T Man Junior Member

    Wellbutrin raises Dopamine as well as norepinephrine. I didn't see that you mentioned this in the very informative article you wrote. Thanks for the good read.
     
  7. #7
    marianco

    marianco Doctor of Medicine

    Ah, the mysteries of Wellbutrin.

    Wellbutrin raises norepinephrine but does not raise dopamine in humans.

    Wellbutrin raises norepinephrine and dopamine in rats. This was erroneously used in psychiatric textbooks to apply to humans. It does not.

    If Wellbutrin raises dopamine, it would be useful, for example, in treating low dopamine conditions such as Parkinson's disease or extrapyramidal side effects of antipsychotic medications. It is not useful.

    I reviewed the literature. Everything points to purely a norepinephrine increase as the mechanism of action of Wellbutrin. Some postulate that this is due to Wellbutrin acting primarily as a norepinephrine reuptake inhibitor. I am not sure of this. It is a very weak norepinephrine reuptake inhibitor. It does not fully explain why it is so potent as an antidepressant. After all these years (20 years since Wellbutrin was first released), we do not have a full description of Wellbutrin's mechanisms of action. Since it is now generic, that research may never be done.
     
    Last edited: Jan 24, 2006
  8. #8
    chap

    chap Junior Member

    any idea if Phosphatidyl Choline is at all a useful libido type supplement?
     
  9. #9
    T Man

    T Man Junior Member

    Once again thanks for the up to date info. A doctor told me that wellbutrin effected dopamine and usually caused anxiety in people prone to it, such as myself.
     

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