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) [L877].

[6] 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).

It is suggested that this compound, similarly to its trans isomer, is an agonist of the vanilloid receptor VR1 (TRPV1) and a neuronal calcium channel blocker.

This effect is followed by a longlasting refractory state – ‘desensitization’ – during which the previously excited sensory neurons become unresponsive to capsaicin and other stimuli.

It is thought that the short-term desensitization is related to capsaicin's ability to block the intra-axonal transport of NGF, SP and somatostatin.

[13][14] Desensitization and depletion of pronociceptive neurotransmitters induce chemical denervation with a loss of function, which is clinically used in osteoarthritis, diabetic neuropathy, psoriasis and others.

[18][19][20] In dorsal root ganglia and the sciatic nerve, zucapsaicin decreases levels of SP and CGRP, indicating that it influences peptidergic afferent neurons via a desensitization mechanism[21][41].

][23][24] In vitro studies demonstrates weak to moderate inhibitory effects on various cytochrome P450 enzymes, although not clinically significant due to low systemic absorption.

[23] 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.

Other adverse effects observed in clinical trials are eye irritation, arthralgia, aggravated osteoarthritis, burning sensation, headache, cough and sneezing.