It's estimated that erectile dysfunction (ED) affects more than 18 million men in the United States alone.1 The majority of those men are over 40 years old, but it can strike no matter what your age. Sometimes ED is an unfortunate side effect of a disease. For instance, men who have diabetes, decreased testosterone levels, high blood pressure, an enlarged prostate, or some other health conditions may get ED. Often times after prostate surgery men experience ED due to nerve damage or other trauma to the male body.2 Sometimes smoking, alcohol use, or certain medications can all cause ED. It can even be the result of everyday pressures such as stress, anxiety, or just nervousness.3 Fortunately, no matter what the cause, Erectile Dysfunction can be successfully treated.4
While some men respond well to oral ED treatments such as Viagra or Cialis, others do not respond to these treatments or have uncomfortable or even dangerous side effects to these medications.5 In those cases custom compounded medications can often be used successfully to treat ED.6
The injectable medications Papaverine, Phentolamine, Alprostadil (Prostaglandin E1), Atropine, Chlorpromazine, and/or Forskolin are used individually or in combination. While an injectable ED medication may sound intimidating or even painful, the truth is, the treatment involves very little discomfort and is an easy and very effective way to treat ED.7
Oral ED Medications
Viagra (Sildenafil) is available as an oral tablet ranging from 25 mg to 100 mg. A starting dose of 50 Mg taken about one hour prior to sexual intercourse has been recommended8. Viagra has been reported as a safe and efficacious treatment for ED, however, it is ineffective in approximately 27 to 35% of the population and has been associated with a variety of adverse effects including headache, flushing, dyspepsia, and adverse interaction with nitrates and inhibitors of cytochrome P450 enzymes.9 Viagra should not be taken in conjunction with nitrate therapy.10
Cialis (Tadalafil) is available as an oral tablet ranging from 5 to 20 mg. The recommended tadalafil starting dose for most men is 10 mg, taken as needed before sexual activity (but not more than once daily). The dose may be increased to 20 mg or decreased to 5 mg, per its efficacy and the man's personal tolerance of the drug11. Cialis's 36-hour effectiveness earned it the nickname, "The Weekend Pill"; like sildenafil, tadalafil is recommended as an 'as needed' medication. Cialis is the only one of the three that is also offered as a once-daily medication.
Papaverine is particularly known as a smooth muscle relaxant and vasodilator. Its principle pharmacological action is as a non-specific vasdilator of the arterioles and capillaries12. Major side-effects include priapism and corporal fibrosis. These side-effects are greatly reduced when papaverine is used in very low dosages and combined with phentolamine and alprostadil.
Phentolamine may provoke a reflex, increasing sympathetic outflow and the release of norepinephrine. 13When phentolamine is used for the treatment of ED, it is often used in combination with other agents (e.g. papaverine) to enhance its efficacy. The combination of phentolamine and papaverine for the treatment of ED has been studied extensively1415. This combination can be efficacious and may induce erections sufficient for sexual intercourse in over 90% of cases.15
Alprostadil (Prostaglandin E1) binds with PGE receptors, and the resultant relaxation response in the smooth muscle is mediated by cAMP16. Little is known about the pharmacokinetics of PGE1 but it is believed that as much as 80% may be metabolized in one pass through the lungs.17 In all probability, this rapid degradation by the lungs accounts for its lack of any significant cardiovascular system side-effects when administered intracavernosally.18 It can also be metabolized in the penis.17 Alprostadil has also been used in combination with other agents, such as papaverine, and the combination was superior to only alprostadil.1920 Alprostadil is available as an intraurethral pellet (MUSE),21 intraurethral gel with penetration enhancers 22, or intracavernosal injection. Numerous studies show that the injection is more efficacious.23
Chlorpromazine is an aliphatic phenothiazine that is used in the treatment of a variety of conditions, from anxiety and nausea to schizophrenia and the hiccups. Discovered in 1951, Chlorpromazine was rapidly implemented across the mental health community due to its powerful effects on several neurotransmitter channels24 and has been called the greatest advancement in psychiatric care of the 20th century.25 An element of its psychoactive profile, as an alpha 1-adrenoceptor-blocking agent, made chlorpromazine a natural candidate in the investigations of medications that could be used off-label in the treatment of erectile dysfunction26 and considerable data have shown it to be analogous in efficacy and adverse effects to phentolamine, capable of bolstering combinations via its inclusion.27
Atropine is a non-selective muscarine agonist that functions by competitively binding to muscarine receptors, a class of acetylcholine receptor involved in the contraction and relaxation of smooth muscle and epithelial tissue throughout various parts of the body.28 These receptors, when activated locally in the penis by acetylcholine molecules, cause the corpus cavernosum to contract29--by inhibiting the absorption of acetylcholine by these receptors into cells in the vasculature of the penis, Atropine effectively relaxes the vessels in the penis and helps in achieving erection.30 While atropine's efficacy when used alone is relatively insignificant and it's use in combination with other injectables does not improve the success rates of a mixture without atropine, it can help reduce the pain30 PGE1 can cause. 31
Forskolin is an adenylate cyclase activator that directly stimulates the enzymes responsible for starting and maintaining erections. Adenylate cyclase activators trigger an increase in cyclic adenosine monophosphate (cAMP) which causes smooth muscle relaxation in the penis. This pharmacologic action enhances penile veno-occlusion and increases the quality of an induced erection.
Forskolin has demonstrated safety and efficacy in patients with vasculogenic impotence resistant to standard 3-agent (phentolamine/papaverine/prostaglandin E1) pharmacotherapy. As reported in the Journal of Urology, 1997 Nov;158(5):1752-8; discussion 1758-9.32 Forskolin acts synergistically with prostaglandin E1 to produce improvement in rigidity and/or erection duration with no adverse events.3334
Vasoactive Intestinal Polypeptide (VIP) is a potent vasodialator and smooth muscle relaxant35. It colocalizes with no synthase in penile nerve fibers and has an inhibitory and relaxation-producing effect on strips of human corpus cavernosum tissue and cavernosal vessels.36 VIP may be the principal neurotransmitter involved in penile erection,37 and also suggests that depletion of this powerful vasodilatory peptide may play a key role in the development of penile impotence.38 Of the 171 patients in a placebo-controlled study treated, 75% responded to VIP/Pentolamine and only 12% to placebo (P<0.001)showing that it was a safe and effective means of treating male ED of primarily nonpsychogenic aetiology.39
Injectable ED Medications
- BiMix: A combination of Papaverine & Phentolamine
- Super BiMix: A highly concentrated version of the standard BiMix Injection
- TriMix: A combination of Papaverine, Phentolamine & Alprostadil (PGE1)
- Super TriMix: A highly concentrated version of the standard TriMix Injection
- QuadMix: Super TriMix with Atropine added
- Super QuadMix: A highly concentrated version of the standard QuadMix Injection
- Custom combinations and concentrations available
Click the following link to view our illustrated guide on how to properly perform Intracavernosal Penile Self Injection.
- 1. Johns Hopkins. Bloomberg School of Public Health. 18 Million Men in the United States Affected by Erectile Dysfunction. N.p., 1 Feb. 2007. Web.
- 2. UCLA. Department of Urology. Dealing with Erectile Dysfunction During and After Prostate Cancer Treatment. 10 Jun. 2009.
- 3. Shamloul R, Ghanem H. Erectile dysfunction. Lancet 2013;381:153-65.
- 4. Montague DK, Jarow JP, Broderick GA, et al. Chapter 1: The management of erectile dysfunction: an AUA update. J Urol 2005;174:230-9.
- 5. Sadeghi-Nejad H, Lim H, Long K, Gilhooly P. Assessment of the efficacy of Viagra (sildenafil citrate) using the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS). Urol Int. 2003;71(1):100-2.
- 6. McCullough AR, Barada JH, Fawzy A, Guay AT, Hatzichristou D. Achieving treatment optimization with sildenafil citrate (Viagra) in patients with erectile dysfunction. Urology. 2002 Sep;60(2 Suppl 2):28-38.
- 7. Baniel J, Isarailov S, Engelstein D, Shmueli J, Segenreich E, Livne PM. Three-year outcome of a progressive treatment program for erectile dysfunction with intracavernous injections of vasoactive drugs. Urology 2000 Oct 1;56(4):647-52
- 8. Viagra (sildenafil citrate) package insert. New York, NY: Pfizer; 2006 Oct.
- 9. Bollinger K, Lee MS. Recurrent visual field defect and ischemic optic neuropathy associated with tadalafil rechallenge. Arch Ophthalmol 2005;123(3):400-1.
- 10. Arruda-Olson AM, Mahoney DW, Nehra A, et al. Cardiovascular effects of sildenafil during exercise in men with known or probable coronary artery disease. JAMA 2002;287:719-725.
- 11. Cialis (tadalafil) package insert. Indianapolis, IN: Lilly ICOS, LLC; 2011 Oct.
- 12. Leungwattanakij S, Flynn V, Hellstrom WJG. Intracavernosal injection and intraurethral therapy for erectile dysfunction. Urol Clin North Am 2001;28:343-354.
- 13. Robertson D, Biaggioni I. Chapter 10. Adrenoceptor Antagonist Drugs. In: Katzung BG, Masters SB, Trevor AJ, eds. Basic & Clinical Pharmacology. 12nd ed. New York: McGraw-Hill; 2012. wwwaccesspharmacycom. Accessed December 5, 2012.
- 14. Shamloul R, El-Dakhly M. Intravavernous Chlorpromazine Versus Phentolamine: A Double-blind clinical coparative Study. Sexual Medicine 2004 Nov;1(3):310-313
- 15. a. b. Shamloul R, Atteya A. Intravavernous soium Nitroprusside (SNP) versus Papaverine/Phentolamine n Erectile Dysfunction: A Comparative Study of Short-Term Efficacy and Side-Effects. Sexual Medicine 2005Jan;2(1):117-120
- 16. Prostin VR Pediatric® (alprostadil injection) package insert. Kalamazoo, MI: Pharmacia and Upjohn Company.; 2006 Apr.
- 17. a. b. Hamberg M, Samuelsson B. On the metabolism of prostaglandin E1 and E2 in man. J Biol Chem 1971;246(22):6713-21.
- 18. Buck, Marcia L. Alprostadil (PGE1) for Maintaining Ductal Patency. Pediatric Pharmacotherapy. 2000;6(9)
- 19. Bachara A, Casabe A, Cheliz G, Romano S, Rev H, Fredotovich N. Comparative study of papaverine plus phentolamine versus prostaglandin E1 in erectile dysfunction. Urology. 1997 Jun;157(6):2132-4.
- 20. Floth A, Schramek P. Intravavernous injection ofp prostaglandin E! in combination with papaverine: enhanced effectiveness in comparison with papaverine plus phentolamine and prostaglandin E1 alone. Urology. 1991 Jan;145(1):56-9.
- 21. Guay AT, Perez JB, Velasquez E, Newton RA, Jacobson JP. Clinical experience with intraurethral alprostadil (MUSE) in the treatment of men with erectile dysfunction. A restrospective study. Medicated urethral system for erection. European Urology. 2000 Dec;38(6):671-6
- 22. Goldstein I, Pavton TR, Schechter PJ. A double-blind, placebo-controlled, efficacy and safety study of topical gel formulation of 1% alprostadil (Topiglan) for the in-office treatment of erectile dysfunction. Urology. 2001 Feb;57(2):301-5
- 23. Linet OI, Ogrinc FG. Efficacy and safety of intracavernosal alprostadil in men with erectile dysfunction. The Alprostadil Study Group. New England Journal of Medicine. 1996 Apr 4;334(14):873-7
- 24. Healy, David. The Creation of Psychopharmacology. Harvard University Press. 2004
- 25. Adams CE, Awad G, Rathbone J, Thornley B, Soares-Weiser K. "Chlorpromazine versue placebo for schizophrenia". Cochrane Database of Systematic Reviews. 2014 Jan 6;1:CD000284. doi: 10.1002/14651858.pub3. Review.
- 26. Naganuma H, Egashira T, Fujii I. "Neuroleptics induce penile erection in the rabbit." Department of Neuropsychiatry, Oita Medical University, Japan. Clinical and Experimental Pharmacology & Physiology. 1993 Mar;20(3):177-83
- 27. Shamloul R, El-Dakhly M, Ghanem H, Gadallah A, Mokhtar H. "Intracavernous Chlorpromazine Versus Phentolamine: A double-blind Clinical Comparative Study. Journal of sexual Medicine. 2004 Oct 13;1(1):310-313
- 28. Rang HP, Dale MM, Ritter JM, Flower RJ. "Ch. 10". Rang and dale's pharmacology. Elsevier Churchill Livingstone, 2007. p. 153.
- 29. Senbel AM, Hashad A, Sharabi FM, Daabees TT. "Activation of muscarine receptors inhibits neruogenic nitric oxide in the corpus cavernosum." Pharmacological Research 2012 Mar;65(3):303-11.
- 30. a. b. Sogan PR, Teloken C, Souto CA. "Atropine role in the pahrmacological erection test: study of 228 patients. Journal of Urology 1997 Nov;158(5):1760-3
- 31. Kunelius P, Lukkarinen O. Intracavernous self-injection of prostaglandin E1 in the treatment of erectile dysfunction. International Journal of Impotence Research. 1999 Feb;11(1):21-4
- 32. Mulhall JP, Daller M, Traish AM, Gupta S, Park K, Salimpour P, Payton TR, Krane RJ, Goldstein I. Intracavernosal forskolin: role in management of vasculogenic impotence resistant to standard 3-agent pharmacotherapy. Urology. 1997 Nov;158(5):1752-8; discussion 1758-9.
- 33. Williams JL fr, Malik KU. Forskolin stimulates prostaglandin synthesis in rabbit heart by a mechanism that requires calcium and is independent of cyclic AMP. Circ Res. 1990 Nov;67(5):1247-56
- 34. Marriott D, Adams M, Boarder MR. Effect of forskolin and prostaglandin E1 on stimulus secretion coupling in cultured bovine adrenal chromaffin cells.
- 35. Kulick RS, Chaiseha Y, Kang SW, Rozenboim I, El Halawani ME (July 2005). "The relative importance of vasoactive intestinal peptide and peptide histidine isoleucine as physiological regulators of prolactin in the domestic turkey". General and Comparative Endocrinology 142 (3): 267–73.
- 36. Conconi MT, Spinazzi R, Nussdorfer GG (2006). "Endogenous ligands of PACAP/VIP receptors in the autocrine-paracrine regulation of the adrenal gland". International Review of Cytology 249: 1–51
- 37. Principal neurotransmitter: Hill JM (2007). "Vasoactive intestinal peptide in neurodevelopmental disorders: therapeutic potential". Current Pharmaceutical Design 13 (11): 1079–89.
- 38. Fahrenkrug J, Emson PC (September 1982). "Vasoactive intestinal polypeptide: functional aspects". British Medical Bulletin 38 (3): 265–70.
- 39. Dinsmore WW, Gingell C, Hackett G, Kell P, Savage D, Oakes R, Frentz GD. Treating men with predominantly nonpsychogenic erectile dysfunction with intracavernosal vasoactive instestinal polypeptide and phentolamine mesylate in a novel auto-injector system: a multicentre double-blind placebo-controlled study. BJU Int. 1999 Feb; 83(3):274-9