Sunday, March 31, 2013

Nitric Oxide, Antidepressants, and "Sexual Side Effects"

Antidepressants, particularly those that affect serotonin metabolism, are famous for causing "sexual side effects." According to package inserts for the drugs, such side effects are relatively uncommon, but that's because patients in clinical trials don't readily volunteer information on sexual problems on their own; you have to ask them about it. When researchers have specifically asked patients about sexual side effects, the topic comes up 58% to 73% of the time, depending on the drug.

If you go looking in the scientific literature for an explanation of why "sexual side effects" happen at all, you'll mostly encounter rather vague, unsatisfying explanations. I did a little digging on my own and came up with what I think is a fairly edifying scientific explanation of what's going on. (From here, it gets a little technical. Bear with me if you can.)

"Sexual dysfunction" covers a lot of ground, and the gaps in our knowledge of the biochemistry underlying things like arousal and orgasm could better be called knowledge in our gaps. However, we do know that nitric oxide (NO) metabolism plays a huge role in stimulatory response. Clitoral erection as well as penile erection depend on production of NO and subsequent NO-induced accumulation of cyclic guanosine monophosphate, or cGMP (see this paper).

Nitric oxide is an interesting molecule. It's a gas at room temperature; soluble in oil as well as water; extremely corrosive; penetrates cell membranes with ease; and is probably the most widely distributed free radical in the human body. For many years, researchers knew of something called the endothelium-derived relaxing factor (EDRF), a substance produced by the inner cell lining of blood vessels, capable of signalling the surrounding smooth muscle to relax (resulting in vasodilation and increasing blood flow). It turns out EDRF and nitric oxide are one and the same. When NO is produced (from arginine and a bunch of cofactors, by the action of an enzyme called, shockingly enough, NO synthase), it triggers massive production of cGMP, which in turn activates protein kinases that (in turn) cause reuptake of calcium ion, which (through a bunch more steps) results in relaxation of smooth muscle.

You wouldn't think relaxation of muscle would be the key to getting an erection going, but that's because you're thinking of the wrong "muscle." Here, we're concerned with blood-vessel smooth muscle. Relaxation of that kind of smooth muscle is crucial to allowing blood to find its way into the structures that ultimately cause a clitoris or penis to become engorged. Without an increase in NO production and all the downstream effects that lead to vasodilation, there's no arousal.

Nitric oxide is not just a vasodilator, though. It's also a gasotransmitter, which is to say a gas that has neurotransmitter properties.

The primary target of SSRIs in the body is the SERT (serotonin transporter) protein, which is the agent responsible for "reuptake" of serotonin. At first glance, it's not at all obvious how serotonin reuptake plays a role in nitric oxide formation. However, an extremely alert group of researchers at the Centre National de la Recherche Scientifique in Montpellier, France, realizing that SERT is known to associate with various proteins having a so-called PDZ domain, and also realizing that neuronal nitric oxide synthase (nNOS) has such a domain, decided to do an experiment. They fused a carboxyl-terminal SERT peptide to Sepharose beads and poured mouse-brain homogenate over the beads to see what stuck. The most abundant protein to stick? None other than nNOS.

The French team found that when nNOS and SERT were coexpressed in a cell line, they bound to each other in vivo. They also found that exposing serotonin to a cell line expressing SERT and nNOS caused the production of NO. Thus, if you blockade SERT (cutting off serotonin reuptake), you interfere with NO production at the source, because nNOS (the enzyme responsible for producing NO) and SERT (the serotonin transporter) are, in fact, joined together, in vivo. (See this PNAS paper for an overview.) Interfering with NO production is bad, of course. No nitric oxide, no erection.

To me, this provides a pretty believable model of how SSRIs interfere with erectile function.

Before leaving the subject of nitric oxide production, I should mention that a huge amount of work has shown that NO metabolism is profoundly impaired in patients with diabetes. The work of the Centre National de la Recherche Scientifique team (outlined above) suggests a mechanism by which SSRIs interfere with NO metabolism. Another connection between SSRIs and diabetes?

And finally: It's thought by some that Minoxidil owes its hair-regrowing effects to the fact that it's a nitric-oxide agonist (Mi-NO-xidil). This suggests that hair loss would be an expected "side effect" of SSRIs. And indeed there are scattered reports of such in the literature.

118 comments:

  1. Very interesting findings Kas. Thx.

    ReplyDelete
    Replies
    1. There is so much misinformation and so many bogus products surrounding penis enlargement that when they discover the solution, no one will believe. So here goes; any male can permanently increase length and girth in the same way a bodybuilder adds mass and becomes larger. As you stress tissue, the body goes into a natural process of creating new cells making you larger. The question is not whether permanent enlargement is possible but instead, how do you safely stress penile tissue to promote cell growth? The answers can be found at MagnumRings.com

      Delete
    2. IEEE Final Year projects Project Centers in India are consistently sought after. Final Year Students Projects take a shot at them to improve their aptitudes, while specialists like the enjoyment in interfering with innovation. For experts, it's an alternate ball game through and through. Smaller than expected IEEE Final Year project centers ground for all fragments of CSE & IT engineers hoping to assemble. Final Year Projects for CSE It gives you tips and rules that is progressively critical to consider while choosing any final year project point.

      JavaScript Online Training in India

      JavaScript Training in India

      The Angular Training covers a wide range of topics including Components, Angular Directives, Angular Services, Pipes, security fundamentals, Routing, and Angular programmability. The new Angular TRaining will lay the foundation you need to specialise in Single Page Application developer. Angular Training

      Delete
    3. Topmedsreview helps you to provide information about prescription drugs that are prescribed to treat various kinds of diseases. We deliver our services in the United States, USA. To place your order as overnight delivery, you can choose your products and place them at any point in time and get it delivered the next day at your doorstep.

      Buy Lexapro Online

      Buy Diazepam Online

      Buy Xanax Online

      buy adderall online
      buy viagra online
      buy xanax online
      buy tramadol online
      buy oxycodone online
      buy oxycontin online
      buy phentermine online
      buy ambien online
      buy hydrocodone online
      buy percocet online
      buy adipex online
      buy cialis online
      buy suboxone online
      buy vicodin online
      buy soma online
      buy norco online
      buy alprazolam online legally
      buy codeine online
      buy methadone online
      buy subutex online
      buy diazepam online
      buy dilaudid online
      buy clonazepam online
      buy levitra online
      buy ultram online
      buy lortab online
      buy roxicodone online
      buy opana online
      buy carisoprodol online
      buy lexapro online
      buy hydromorphone online
      buy demerol online
      buy flexeril online
      buy lorazepam 1mg online
      buy meridia online
      buy darvocet online
      buy ultracet online
      buy green xanax bars
      buy yellow xanax bars online
      buy darvon online
      buy lorcet online

      Delete
  2. Wish I knew all this before taking the damn ssris. I'm so angry at my pdoc. My condition actually doesn't require being on an AD.

    ReplyDelete
  3. This comment has been removed by the author.

    ReplyDelete
  4. This comment has been removed by the author.

    ReplyDelete

  5. Erectile dysfunction was ruining not just my sex life but also my marriage.

    Divorce seemed inevitable.

    I was going to lose everything, even my kids...

    Until I discovered an amazing life hack that allows me to get my dick diamond hard, and ready for hot passionate sex with my wife on demand!

    This is not a joke. You CAN beat ED safely, and naturally without wasting money on dangerous pills for the rest of your life.
    Watch the video below and learn how I did just that, and how YOU can too!

    ===> [Life Hack] One Amazing Trick to Get Hard on Demand <=====

    The funny thing is, even though my marriage is saved, I almost wish I was single again with my newfound explosive sex drive and libido.
    I hope my wife doesn't divorce me for wearing her out every night... ;)

    It's amazing that the secret to regaining your sexual vigor and killing ED permanently is all-natural, easy, and affordable.

    If you're wasting money on pumps, pills, injections, or disgusting food combinations, stop right now.

    The answer to your erectile dysfunction problems has been right in front of you this entire time...

    Use the link, watch the video. You won't believe how simple turbo-charging your penis, and beating ED really is.

    ===> The #1 Instant Erection Life Hack ? A Natural ED Killer <=====

    P.S. Getting rid of ED isn't just about better sex, it's about regaining your pride and self-respect as a man.

    Watch the video and learn how easy it is to go from having a "wet noodle" to rocking a massive diamond hard erection your partner will want inside her every night!

    ===> Proof Of REAL Growth <=====

    ReplyDelete
  6. You define your thought classically by this blog, thank you so much for sharing such an amazing blog. Get website designing services by ogen infosystem in delhi, india.
    SEO Service in Delhi

    ReplyDelete
  7. Want to buy African dresses online? Koshieo provides the best natural mens African Clothing to make your mark this weekend.

    ReplyDelete
  8. Keep more data about this related blog, by and large this is significant for me. Get the best Mutual Fund Advisor and Investor premiums at Mutualfundwala.
    Mutual Fund Agent

    ReplyDelete
  9. I like the way you had explained things. Thanks for sharing with us. Really appreciated. SEO Agency India

    ReplyDelete
  10. Thanks for sharing this valuable information with us...
    India Tour Packages

    ReplyDelete
  11. Nice blog. This is very useful and quite different topic.
    Thanks
    mobile application development

    ReplyDelete
  12. Thanks for sharing this blog.
    SEO Agency India

    ReplyDelete
  13. Very useful information.
    Thanks for sharing
    SEO Services India

    ReplyDelete
  14. Very unique article
    Thanks for sharing such knowledge
    Green Energy Consultancy Services

    ReplyDelete
  15. This so nice and very useful blog
    Thanks for sharing
    Huntley IL funeral home and cremation

    ReplyDelete
  16. L-arginine is found in red meat, poultry, fish, and dairy products. It can also be made in a laboratory and used as medicine. L-arginine is used for heart and blood vessel conditions including congestive heart failure (CHF), chest pain, high blood pressure, and coronary artery disease.

    ReplyDelete
  17. Thanks For Sharing!!!!!!
    Buy Silicone Sex Doll from Online store at LoveDollPalace based US Company. Browse our collection of realistic, inflatable life-size love dolls. Order yours today!

    ReplyDelete
  18. Thanks to share this best blog with us. please visit Alejandro Saez-Blanco for latest updates of USA.

    ReplyDelete
  19. Your blog really nice. Its sound really good. I am very time read your blog. Thanks for the sharing this blog with us. Keep it up.

    best mobile app development companies in India
    mobile app development company in India

    ReplyDelete
  20. Thanks Really Interesting Post
    a2z life style

    ReplyDelete
  21. Nice blog, Get School Bus Painting and Fleet Painting at Kalakutir Pvt Ltd in Delhi, India.
    School Bus Painting

    ReplyDelete
  22. This comment has been removed by the author.

    ReplyDelete
  23. We are really grateful for your blog post. Nice Blog! Experience the Best Assignment Writing Services at
    cheap assignment help
    cheap assignment help Australia

    ReplyDelete
  24. TruckingCube company provides the best truck rental service to its customers. Read more about their services.

    Transportation Service
    Moving Truck

    ReplyDelete
  25. Thanks to share this best information with us. Please visit here for latest techniques and more about web development company in all over the world.
    Web Development Company

    ReplyDelete
  26. Thnaks to share this best information with us. Please visit here to get more about best Briquette Machine and Micromax Combo and Sawdust Machine. You may visit our website. Wood Log Chipper

    ReplyDelete
  27. Absolutely Clean is a popular origination that provides services like crime scene clean up, blood cleanup, biohazard cleanup Craig Colorado etc.

    ReplyDelete
  28. This is a great inspiring article. I am pretty much pleased with your good work.You put really very helpful information.
    Topxlisting

    ReplyDelete
  29. Thank you for sharing this information medical device sales career

    ReplyDelete
  30. This comment has been removed by the author.

    ReplyDelete
  31. I blog quite often and I genuinely appreciate your content. Your article has really peaked my interest. I'm going to take a note of your site and keep checking for new information about once a week. I subscribed to your RSS feed too. hp battery replacement center

    ReplyDelete




  32. PSl 2020 is nearly to coming in pakistan in February 20. The most awaited and the Popuplar event that is gonna be start. So Get ready and enjoy all the pakistan super laegaue live streaming, schedule, fixture and the other teams details. You can watch all the match updates and the Online ball by ball updates.

    Psl live streaming 2020

    ReplyDelete
  33. Nitric Oxide, Antidepressants amazing article I like this writing way. Your post was good and the information that you give in your post, that was really cool. I like it very much. Thanks for posting this great information with us. Please share more information and I will bookmark to my blog. Web Design Company Dubai it provides best design service.

    ReplyDelete
  34. Thank you for such a well written article. It’s full of insightful information and entertaining descriptions. Your point of view is the best among many. Fullmetal Alchemist Jacket

    ReplyDelete
  35. Your article is such an informative article. It is glad to read such those articles thanks for sharing. First Aid Usmle

    ReplyDelete

  36. This is a great blog posting and very useful.SEO Expert Dubai

    ReplyDelete
  37. Very informative put up! This submit gives sincerely exceptional statistics. I locate that this put up is simply first rate. Thanks for this explanation and very nice information.

    office.com/setup
    mcafee.com/activate

    ReplyDelete
  38. The information you have posted is very useful. I really enjoy reading and also appreciate your work. Please keep inspiring more readers!
    Front End Developer
    full stack developer
    ios developer

    ReplyDelete
  39. Great Experience the Best Assignment Writing Services at
    Academic Essays Help

    ReplyDelete
  40. Sizde yetişkin kullanıcıları bulabileceğiniz fikriyle gelmek istiyorsanız aramızda her zaman yeriniz vardır. Ancak odalarımız sapıkça düşüncelerle gelen kullanıcılara açık değildir şimdiden bilgilendirmesini yapalım. Sizlerin güvenliğini ve aile ortamı içerisinde yeni arkadaşlarla tanışma imkanınızı sağlamakla görevliyiz. Görevimizin ve sorumluluklarımızın farkında olarak sizlere hizmet veriyoruz. Sizleri de aramıza bekliyoruz.
    https://forum.hayalsohbet.net
    https://izmir.hayalsohbet.net
    https://hayalsohbet.net/sohbet
    https://hayalsohbet.net/mobil

    ReplyDelete
  41. Buy Sex toys in India with with mytimetoy we are #1 seller for sex toys for women, sex toys for men, sex toys for couple and sex toys for bdsm we have high quality products for 100% Satisfaction.

    ReplyDelete
  42. Shahwalia Associates is the firm with Architects in Delhi. Our highly experienced Interior Desinger in Noida ners understand all your needs and provide you with the best solutions in your budget.

    ReplyDelete
  43. DRH ReJoint is the flagship product of Functional Herbals LLC, a company dedicated to developing only the most effective nerve healing supplements, joint pain supplements for improved health we have natural solutions for chronic pain treatment, knee lock pain.

    ReplyDelete
  44. Its very good to see such a nice and informative article, this article really getting me an aspiration to do the same as you. Keep going on Admin and thank you for the content.
    seo Agency in Sharjah
    seo Agency in Dubai
    seo Agency in Ajman
    SEO Agency in Ras Al Khaimah
    SEO Agency in Abu Dhabi
    SEO Agency in Al Ain

    ReplyDelete
  45. Neinstein’s team of personal injury lawyers in Toronto has expertise in many aspects of Canadian personal injury law. We fight to ensure our clients and their families receive the compensation, care and support they deserve. We believe it’s the job of a trauma lawyer to act as your advocate and trusted advisor through the complex legal, medical and insurance issues related to your recovery. As a result of this commitment, our firm has some of the most recommended car accident lawyer in Toronto and all of Ontario.

    ReplyDelete
  46. Wow such an amazing content keep it up. I have bookmarked your page to check out more informative content here. Check this out Cyberpunk 2077 Jacket for yourself or to gift someone you may love.

    ReplyDelete
  47. Its very good to see such a nice and informative article, this article really getting me an aspiration to do the same as you. Keep going on Admin and thank you for the content.
    SEO Agency in Dubai

    ReplyDelete
  48. Hi Admin thanks for providing such an informative article about the topic, actually I have read many articles but this is unique from others. Really I have enjoyed lot reading this. Thank you so much, keep sharing such nice articles.
    Desert Safari Dubai
    Desert Safari Sharjah
    Desert Safari Ajman

    ReplyDelete
  49. I genuinely appreciate your content. Your article has really peaked my interest Crocodile Dundee Vest the product every person is looking for check this out

    ReplyDelete
  50. cyberpunk jacket The author, John T., who lives in London UK writes: The real value comes from the concept they have picked up by using different methods to determine what people are actually interested.

    ReplyDelete
  51. Thanks for sharing this articles this is really helpful for me. Check this amazing Stripes Black Leather Jacket available in special discount and with free shipping as well.

    ReplyDelete
  52. Waist trainers those are also used by models as lower tummy fat waist trainer . Introducing you the best corset belts to get rid of your curvy body fat. These waist trainers helps to get your body in shape within few days. Most of the models use these trainers to get their body in hour glass shape. You can also have multiple choices to select corset for your body type.

    ReplyDelete
  53. how to lower your belly naturally in 7 days, Get your answer by using the waist trainer for lower belly fat that will help you to control whole of your tummy area and to get the best shape of your body . Waist trainer can also be used during your exercise. It help to reduce the fat naturally within few days.

    ReplyDelete
  54. Waist trainers are used to control tummy and back fat. It helps to reduce the fat from the lower belly and love handles. These trainer belts can be wear under clothes and reduce tummy fat within few days. Waist trainers are comfortable enough to wear during workout that boost your fat lose process.

    ReplyDelete
  55. We are really grateful for your blog post. Thanks for the information. It's very useful. Check this amazing coupon. Hoverboard 360 Coupon

    ReplyDelete
  56. Everything in this content is in proper order. One can easily learn so much from your articles. Thank you for keeping us informed. An outstanding share!
    Erectile Dysfunction Expert

    ReplyDelete
  57. Thanks for the excellent content. Can I share this with my friends? They are also looking for content like this!
    custom embroidery nyc
    embroidery services nyc
    embroidery stores nyc
    one point office supplies in New york
    embroidery supplies nyc

    ReplyDelete
  58. Green Earth Homes continuously improves our service to customers and being responsive to their needs by constructing sustainable, safe, high quality and cost effective builders sunshine coast, through a process of consultation and innovation.
    At Life Law Solutions, we understand your time is precious and our experienced team will provide solutions to get you through the legal system as efficiently as possible. Our estate lawyers will listen to your concerns and tailor a solution to meet your personal needs. Our goal is to achieve the best possible outcome with minimal disruption to your life. We specialize in family and relationship law, mediation, wills and estate planning and administration.
    A good Naturopath is someone who looks at many different aspects of your life and works on all of them. At the naturopaths in Newcastle, the Naturopaths address all of these things and may combine them to steer you towards Better Health Naturally.

    ReplyDelete
  59. If you are looking for plus size clothing online, we can help you. We are the no1 apparel store for you in the United States for plus size clothing. We have a wide collection of plus size women clothing. Contact us now. plus size clothing online

    ReplyDelete
  60. Thanks for the excellent content. Can I share this with my friends? They are also looking for content like this!
    auger extensions
    canola harvester
    header farming
    forage harvest
    farm machinery
    agri spares

    ReplyDelete
  61. Established in 2020, Kooshen has been formed with a vision to provide a German Quality product to users of Short Cycle Lamination Press’s globally. With 120+ companies trusting our Cushion Pads we have an enviable track record and expanding at a phenomenal pace. COVID19 has disrupted supply chains for companies & companies looking for non-Chinese alternatives, thereby, leading to a rapid expansion for our brand “Kooshen”.

    ReplyDelete

Add a comment. Registration required because trolls.