Resiniferatoxin promotes inflow and prolongs channel opening, which causes TRPV1 fibers or cell bodies to undergo acute pain-inducing cytotoxicity [1].

Resiniferatoxin (2 μg/10 μl; intrathecally into the T2/T3 area; causes cardiomyopathy 4 weeks post-coronary blockage) reduces overactivated CSNA and dramatically and indirectly abolishes marker expression in the dorsal horn (TRPV1 and nortonin-inducible gene-related peptide). Resiniferatoxin decreases the susceptibility of ventricular arrhythmias and dramatically reverses the lengthening of action episode duration (APD) and APD alternation [2].

Rodent Trigeminal Ganglion Injection (Rat):** Resiniferatoxin was microinjected unilaterally into the trigeminal ganglia using a transcranial stereotaxic approach or a percutaneous approach via an electrical-stimulation needle inserted through the infraorbital foramen. A dose of 200 ng was used. [1]
* **Nonhuman Primate Trigeminal Ganglion Infusion:** Resiniferatoxin solution (20 μL of 0.1 mg/mL concentration) was infused unilaterally into the trigeminal ganglia. [1]
* **Rodent Intracisternal Injection (Mouse):** Resiniferatoxin (100 μg) or vehicle was injected into the cerebrospinal fluid at the cisterna magna. [1]
* **Rodent Intrathecal Injection (Rat):** Resiniferatoxin was administered intrathecally to target the ganglionic nerve roots. Inflammation was induced by intraplantar injection of 100 μL of 2% carrageenan. Pain sensitivity was tested with intraplantar capsaicin injection and thermal paw withdrawal latency. [1]
* **Canine Intrathecal Injection:** Under general anesthesia, resiniferatoxin was administered intrathecally into the cisterna magna at doses of 0.1, 1.2, or 3.0 μg/kg. For the bone cancer study, dogs were randomized to standard of care alone or standard of care plus a single intrathecal injection of resiniferatoxin (1.2 μg/kg). All dogs in the RTX group were anesthetized for the procedure and hospitalized overnight. [1]
* **Behavioral Testing (Canine):** Paw withdrawal latency to a radiant thermal stimulus was measured in unrestrained dogs placed on a glass-top table. The heat source was positioned under a paw and terminated when the dog lifted its limb, with a maximum exposure of 20 seconds. Lameness was evaluated by a blinded orthopedist through video analysis. Owner pain assessments and activity monitoring via collar-worn accelerometers were also used. [1]
* **Human Clinical Trial Protocol:** In a Phase I clinical trial for patients with advanced cancer, an intrathecal catheter is placed, and resiniferatoxin (3 to 26 μg) is injected under general anesthesia to prevent the acute pain associated with TRPV1 activation. Serial electrocardiograms, brain and spine MRIs, eye exams, blood analyses, and neurological exams are performed pre- and post-injection. Pain, quality of life, activity, and mental status are assessed using standardized tools. [1]

[1]. Brown DC. Resiniferatoxin: The Evolution of the "Molecular Scalpel" for Chronic Pain Relief. Pharmaceuticals (Basel). 2016;9(3):47. Published 2016 Aug 11.

[2]. Resiniferatoxin reduces ventricular arrhythmias in heart failure via selectively blunting cardiac sympathetic afferent projection into spinal cord in rats. Eur J Pharmacol. 2020;867:172836.

Resiniferatoxin is a heteropentacyclic compound with the molecular formula C37H40O9 found in plants of the genus Euphorbia. It is an agonist of transient receptor potential cation channel subfamily V member 1 (TRPV1). It possesses multiple functions, including TRPV1 agonist, plant metabolite, neurotoxin, and analgesic. It is a diterpenoid, orthoester, tertiary α-hydroxy ketone, phenolic compound, monomethoxybenzene, organic heteropentacyclic compound, carboxylic acid ester, and enone. Resiniferatoxin (RTX) is a naturally occurring, highly potent capsaicin analog that activates vanillin receptors in primary afferent sensory neuron subsets involved in nociception (the transmission of physiological pain). Resiniferatoxin has been reported to exist in Euphorbia unispina and Euphorbia resinifera, with relevant data available. Resiniferatoxin is a naturally occurring capsaicin analog found in the latex of Euphorbia resinifera and possesses analgesic activity. Resiniferatoxin (RTX) binds to and activates transient receptor potential (TRP) vanillin receptor 1 (TRPV1), a non-selective cation channel on the plasma membrane of primary afferent sensory neurons. This increases cation permeability, leading to an influx of calcium and sodium ions. This causes membrane depolarization, producing a stimulatory effect, followed by desensitization of the sensory neuron, thereby inhibiting signal transduction in the afferent pain pathway and producing an analgesic effect. TRPV1 is a member of the transient receptor potential (TRP) superfamily and is a heat- and chemically sensitive calcium/sodium ion channel selectively expressed in a subset of primary pain-sensing afferent neurons.

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Pharmacological Indications
It has been studied for the treatment of interstitial cystitis and urinary incontinence.

628.267

57444-62-9

5702546

White to off-white solid powder

1.35g/cm3

768.7ºC at 760mmHg

240.3ºC

1.643

4.744

2

9

9

46

1330

8

O1C2(C([H])([H])C3C([H])=C([H])C([H])=C([H])C=3[H])O[C@@]3(C(=C([H])[H])C([H])([H])[H])C([H])([H])[C@@]([H])(C([H])([H])[H])[C@]41[C@]1([H])C([H])=C(C([H])([H])[H])C([C@]1(C([H])([H])C(C([H])([H])OC(C([H])([H])C1C([H])=C([H])C(=C(C=1[H])OC([H])([H])[H])O[H])=O)=C([H])[C@@]4([H])[C@@]3([H])O2)O[H])=O

DSDNAKHZNJAGHN-MXTYGGKSSA-N

InChI=1S/C37H40O9/c1-21(2)35-17-23(4)37-27(33(35)44-36(45-35,46-37)19-24-9-7-6-8-10-24)14-26(18-34(41)30(37)13-22(3)32(34)40)20-43-31(39)16-25-11-12-28(38)29(15-25)42-5/h6-15,23,27,30,33,38,41H,1,16-20H2,2-5H3/t23-,27+,30-,33-,34-,35-,36-,37-/m1/s1

[(1R,2R,6R,10S,11R,13S,15R,17R)-13-benzyl-6-hydroxy-4,17-dimethyl-5-oxo-15-prop-1-en-2-yl-12,14,18-trioxapentacyclo[11.4.1.01,10.02,6.011,15]octadeca-3,8-dien-8-yl]methyl 2-(4-hydroxy-3-methoxyphenyl)acetate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~50 mg/mL (~79.53 mM)

Solubility in Formulation 1: ≥ 1.25 mg/mL (1.99 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 1.25 mg/mL (1.99 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)