Papaverine
Papaverine is a non-selective phosphodiesterase inhibitor and opium-poppy alkaloid used as an intracavernosal vasodilator for erectile dysfunction, usually as part of bimix/trimix injection mixtures alongside phentolamine and alprostadil. It predates the oral PDE5 inhibitors and remains a workhorse of injection therapy for men who fail oral drugs.
01 Overview
Papaverine relaxes vascular and cavernosal smooth muscle through non-selective phosphodiesterase inhibition (raising both cAMP and cGMP) and direct calcium-channel effects. Injected into the corpus cavernosum it produces an erection independent of nerve signalling, which is why it works when oral agents do not. It is rarely used alone now, more often combined with phentolamine (bimix) or with phentolamine and alprostadil (trimix) to improve efficacy and lower each drug's dose.
As an injection therapy it carries the same core risks as alprostadil — priapism and, with repeated use, penile fibrosis — plus a risk of elevated liver enzymes with systemic exposure. It is a prescription compounded therapy, not an oral lifestyle drug.
02 Mechanism
Non-selective phosphodiesterase inhibitor raising cAMP and cGMP, plus direct smooth-muscle relaxant activity, producing NO-independent cavernosal vasodilation.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Intracavernosal (alone) | 7.5–60 mg | IM | Injected into the corpus cavernosum, titrated. Often replaced by lower doses within a mix. (Route intracavernosal; closest enum INTRAMUSCULAR.) |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Erection independent of PDE5 pathwayProduces erection via direct smooth-muscle relaxation; effective when oral PDE5 inhibitors fail, especially combined in bimix/trimix. | high response in mixes | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Elevated liver enzymesTransient rises in transaminases have been reported with papaverine. | Mild | Uncommon | Clinical | |
| Penile fibrosisFibrous nodules or curvature with long-term repeated injection, somewhat more than with alprostadil. | Moderate | Uncommon with repeated use | Clinical | |
| PriapismProlonged erection >4 h is a urological emergency; papaverine-containing mixes carry a notable priapism risk. | Severe | Uncommon but urgent | Clinical |