Zucapsaicin
Zucapsaicin Uses, Dosage, Side Effects, Food Interaction and all others data.
Zucapsaicin, the cis-isomer of capsaicin, is a topical analgesic used to treat osteoarthritis of the knee and other neuropathic pain. It is a modulator of transient receptor potential cation channel subfamily V member 1 (TRPV-1), also known as the vanilloid or capsaicin receptor 1, that reduces pain and improves articular functions. Zucapsaicin has also been evaluated for the management of several conditions manifested by chronic nerve pain. These conditions include herpes simplex (HSV) infections, cluster headaches, migraine, and osteoarthritis of the knee. Zucapsaicin was approved by the Health Canada in 2010 as topical cream marketed under the brand name Zuacta but currently not FDA-approved.
Zucapsaicin mediates an antinociceptive action via acting as an agonist at TRPV1. TRPV1 play an important physiological role of transducing chemical, mechanical and thermal stimuli as well as pain transduction, and participate in pain modulation and perception. They are mainly distributed in C sensory nerve fibers as well as Aẟ fibers to transmit sensory information involving inflammatory and neuropathic pain, and activation of these channels releasesomatostatin, calcitonin gene-related peptide (CGRP) and other neuropeptides (neurokinin A, kassinin), leading to neurogenic inflammation . Zucapsaicin is also reported to affect the peptidergic afferent neurons via a desensitization mechanism to decrease the levels of dorsal root ganglia and sciatic calcitonin gene-related peptide (CGRP) and substance P (SP) .
| Trade Name | Zucapsaicin |
| Generic | Zucapsaicin |
| Zucapsaicin Other Names | (Z)-Capsaicin, cis-Capsaicin, Civamide, Zucapsaicin |
| Type | |
| Formula | C18H27NO3 |
| Weight | Average: 305.4119 Monoisotopic: 305.199093735 |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Zucapsaicin is a topical analgesic used as an adjunct to relieve severe pain of osteoarthritis of the knee in selected adult patients.
Indicated to be used in conjunction with oral COX-2 inhibitors or NSAIDs for the relief of severe pain in adult patients with osteoarthritis of the knee, not controlled with oral COX-2 inhibitors or NSAIDs alone, for a duration of no more than three months.
Zucapsaicin is also used to associated treatment for these conditions: Severe Pain
How Zucapsaicin works
Zucapsaicin excites and desensitizes C-fibers via agonist at TRPV1 on nociceptive neurons. It binds to intracellular sites and initially stimulates the channels, causing burning sensation. Activation of TRPV1 results in calcium influx and sodium, which leads to cell depolarization. Hypersensitization by zucapsaicin is then followed by reduced sensitivity and persistent desensitization (tachyphylaxis) of the channels via various pathways. Densentiziation is thought to be dependent on intraceullar levels of calcium . Decreased TRPV1 channel action and release of inflammatory neuropeptides induces an analgesic effect, and pain relief . Zucapsaicin activates calcineurin and calcium-dependent protein kinase C isoforms which results in phosphorylation of TRPV1. Phosphorylation of TRPV1 enhances reponsivity to zucapsaicin by potentiating capsaicin- or proton-evoked responses and reducing the temperature threshold for TRPV1 activation . Studies suggest that zucapsaicin is involved in activation of phospholipase C with the subsequent phosphatidylinositol 4,5-biphosphate (PIP2) hydrolysis, which results in TRPV1 inactivation . Tachyphylaxis or persistent desensitization is reversible, and involves the downregulation of proalgesic substances (such as SP) and upregulation of analgesic peptides .
Toxicity
Most common adverse effects involved application site reactions such as transient burning and warm sensation. Other adverse effects observed in clinical trials are eye irritation, arthralgia, aggravated osteoarthritis, burning sensation, headache, cough and sneezing. Oral LD50 in mouse is >87.5 mg/kg in male and 90 mg/kg in males and >60 mg/kg in females .
Food Interaction
No interactions found.Elimination Route
Zucapsaicin displays low systemic absorption and localizes at the area of application. In animal studies, systemic absorption is 0.075% .
Half Life
In rats, the elimination half life of zucapsaicin and its metabolites is approximately 7 to 11 hours .
Elimination Route
In rat studies, zucapsaicin and its metabolites are slowly excreted into urine and feces (up to 2/3), with minimal elimination via exhalation following dermal administration .
Innovators Monograph
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