preprints.org > medicine and pharmacology > pharmacology and toxicology > doi: 10.20944/preprints202305.1179.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 16 May 2023 / Approved: 17 May 2023 / Online: 17 May 2023 (04:16:16 CEST)

The tobacco cembranoid (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (4R) is known to induce neuroprotection against brain ischemia, systemic inflammation, Parkinson's disease, and organophosphate toxicity in rodents. Studies examining the compound's safety in male and female Sprague Dawley rats demonstrated no significant side effects after a single injection of 4R at various concentrations (6, 24, or 98 mg/kg). To evaluate the neurotherapeutic feasibility of 4R for clinical trials, we have assessed the safety of this compound in nonhuman primates. We investigated whether 4R induces toxicity in male Macaca mulatta when administered for 11 consecutive days via intravenous injection at a dose of 1.4 mg/kg. Electroencephalogram, somatosensory evoked potential, and transcranial motor evoked potentials were measured at days 0, 4, 8, and 12 and remained unaffected during the experimental study. Spontaneous behavior was not affected between the groups. Small histopathological changes in the organs were observed in some animals, both treated and non-treated; thus, these changes cannot be attributed to 4R. Minor hematological and blood composition variations with no clinical significance were detected in the experimental animals. In conclusion, our data support previous findings that 4R is a non-toxic compound that proved safe in nonhuman primates during the given period and dose.

cembranoids, safety, nonhuman primates, 4R

Medicine and Pharmacology, Pharmacology and Toxicology

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