This page describes pharmacological agents that may have legal restrictions, side effects, and drug interactions in your jurisdiction. Information is for educational research only — consult a clinician before considering any compound.
Nortadalafil
N-desmethyl analog of tadalafil — designer adulterant rather than regulated drug; FDA-flagged in counterfeit "natural male enhancement" supplements; tadalafil dominates it on every axis
Aliases (15)
Overview
What is Nortadalafil?
Nortadalafil is the N-desmethyl structural analog of tadalafil (the FDA-approved Cialis). It is NOT a tadalafil prodrug and NOT a substantial in-vivo tadalafil metabolite — tadalafil's primary metabolic route is methylenedioxy ring opening, not N-demethylation. Nortadalafil exists almost entirely as a designer compound made directly in chem labs: sold via research-chemical vendors with 'not for human consumption' disclaimers, and most commonly encountered as an undeclared adulterant in counterfeit 'natural male enhancement' supplements that the FDA repeatedly recalls.
Key Benefits
None over tadalafil for any user with legitimate or established gray-market access to the parent compound. Mechanism is extrapolated PDE5 inhibition with ~half the in-vitro receptor potency (IC50 ~11-12 nM vs tadalafil's ~5 nM), an unverified ~6 hour half-life (vs tadalafil's 17.5 hr), and unknown bioavailability / Cmax / Tmax / food effect. The shorter half-life eliminates tadalafil's daily-dose steady-state advantage. The price gap is zero — Indian-pharmacy generic tadalafil 20mg is $0.30-0.80/pill from the same vendors that sell modafinil.
Mechanism of Action
Selective PDE5 inhibition (extrapolated by structural analogy) → cGMP accumulation in vascular smooth muscle → NO-mediated vasodilation in penile, pulmonary, prostatic, peripheral, and possibly cerebral vasculature. Lacks the N-methyl group on tadalafil's piperazinedione ring; this single methylation difference is the entire structural distinction. Selectivity vs PDE6 / PDE11 not characterized; class side-effect profile (headache, back pain, NAION risk, priapism risk, severe hypotension with nitrates) assumed to carry over.
Pharmacokinetics
Peptide Interactions
(nitroglycerin, isosorbide, "poppers"/amyl nitrite) — ABSOLUTE CONTRAINDICATION. Severe, potentially fatal hypotension. This is the headline FDA warning for …
(tamsulosin, doxazosin, terazosin) — additive hypotension
contraindicated; redundant pathway hit
(ketoconazole, ritonavir, clarithromycin, grapefruit) — assumed AUC raise, but unmeasured for nortadalafil specifically
(rifampin, carbamazepine, St. John's Wort) — assumed exposure drop
Quality Indicators
COA from research-chem vendor with HPLC purity ≥98%
If sourced as research chemical, look for vendor-provided Certificate of Analysis with HPLC trace, mass spec confirmation, and lot-specific testing. Even with COA, this is gray-market — verification is partial.
Vendor-stated purity without lot-specific COA
Generic '99% purity' claims without lot-matched analytical data are common. Designer-adulterant variants (N-cyclohexyl, N-cyclopentyl, 2-hydroxypropyl nortadalafil) have been substituted for nortadalafil and vice versa — Liu 2023 and Xu 2016 document this directly.
Unbranded capsule from "natural male enhancement" supplement
FDA recall pattern: Sustain, Schwinnng, Arize, Endurea, MR.7 SUPER 700000, Vitality. Counterfeit supplements often co-contain sildenafil + tadalafil + nortadalafil and undisclosed contaminants. ZERO purity guarantee.
Sourced from sketchy Amazon listing or direct-to-consumer 'horny goat weed' product
Largest real-world exposure pathway is unintentional — consumer buys an 'all-natural' capsule that contains undeclared nortadalafil. The FDA recalls documented exactly this distribution channel repeatedly through 2024.
Visible purity issues (color variation, particulate, off odor)
Standard non-GMP manufacturing risks: solvent residue, heavy metal contamination, intermediate carryover. RC-vendor product with visible inconsistency = stop.
What to Expect
- Onset~30-60 min oral (faster than tadalafil per gray-market reports — consistent with the more polar / more rapidly absorbed structural argument)
- Peak~1-3 hr
- Tapertrails out by ~10-12 hr
Side Effects & Safety 4
Side Effects
- 1Headache (10-15% in tadalafil PRN dosing)
- 2Back / glute myalgia (PDE11 cross-reactivity carries over structurally)
- 3Dyspepsia, nasal congestion, flushing
- 4Limb pain, mild visual disturbance, orthostatic dizziness
When to Stop
- NAION (sudden vision loss) — class-wide PDE5i risk; stop immediately for any visual change
- Sudden sensorineural hearing loss — same protocol
- Priapism (>4 hr erection) — ER if it occurs
- Severe hypotension with nitrates — absolute contraindication (this is why FDA recalls these supplements: cardiac patients on nitroglycerin who unknowingly take "natural" capsules containing undeclared nortadalafil are at *life-threatening* risk)
- Wrong-compound risk: RC vendors routinely mislabel; Liu 2023 documented N-cyclohexyl nortadalafil masquerading as nortadalafil.
- Solvent residue, heavy metal, intermediate contamination: standard non-GMP manufacturing risks.
- Undisclosed-co-adulterant risk: counterfeit supplements often carry sildenafil + tadalafil + nortadalafil simultaneously — Tucker 2018 documented multi-PDE5i contamination as common.
- Mislabeled "natural" supplements bought without knowing: by far the largest real-world exposure pathway. A user-archetype health-conscious 20yo who *unknowingly* picks up a "horny goat weed" capsule from Amazon may end up with nortadalafil exposure — without any of the safeguards he'd put in place if he were intentionally dosing tadalafil.
References
Liu et al. 2023 — Isolation and characterization of a novel tadalafil analogue adulterant, N-cyclohexyl nortadalafil, in a dietary supplement (J Pharm Biomed Anal, PMID 36841095)
analytical-chemistry detection of designer-adulterant nortadalafil variants
View StudyXu et al. 2016 — Isolation and characterization of a tadalafil analogue, N-cyclopentyl nortadalafil in health supplement (J Pharm Biomed Anal, PMID 26580820)
earlier designer-adulterant characterization
View StudyJin et al. 2024 — UPLC-MS/MS-Based Target Screening of 90 PDE5 Inhibitors in 5 Dietary Supplements (Molecules, PMID 39125006)
detected 2-hydroxypropyl nortadalafil in nutritional wine; broad screening framework
View StudyLi, Xu, Moezzi 2021 — Identification of Erectile Dysfunction Drugs in Dietary Supplements by LC Ion Trap MS (J Diet Suppl, PMID 32351143)
LC-MS detection methodology including nortadalafil class
View StudyTucker et al. 2018 — Unapproved Pharmaceutical Ingredients Included in Dietary Supplements Associated With FDA Warnings (JAMA Network Open, PMID 30646238)
776 contaminated supplements 2007-2016, sexual-enhancement category dominant
View StudyFDA — Today The World Recalls Sustain and Schwinnng (Feb 2024) — undeclared tadalafil + nortadalafil
FDA — Today The World Recalls Arize Herbal (Feb 2024) — undeclared nortadalafil
Ring et al. 2005 — Effect of Tadalafil on CYP3A4-mediated Clearance (Clin Pharmacol Ther)
establishes tadalafil's primary metabolic route is methylenedioxy ring opening to catechol, NOT N-demethylation; supports framing that nortadalafil is a synthetic analog rather than an in-vivo tada…
View StudyTadalafil prescribing information (FDA label, Cialis)
class PK / safety reference for the parent compound
View StudyHow was your experience with this compound?
Anonymous · one vote per session · results below at 5+ votes.
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