scholarly journals Proof-of-Concept for the Analgesic Effect and Thermoregulatory Safety of Orally Administered Multi-Target Compound SZV 1287 in Mice: A Novel Drug Candidate for Neuropathic Pain

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 749
Author(s):  
Ádám István Horváth ◽  
Nikolett Szentes ◽  
Valéria Tékus ◽  
Maja Payrits ◽  
Éva Szőke ◽  
...  

SZV 1287 (3-(4,5-diphenyl-1,3-oxazol-2-yl)propanal oxime) is a novel multi-target candidate under preclinical development for neuropathic pain. It inhibits amine oxidase copper containing 3, transient receptor potential ankyrin 1 and vanilloid 1 (TRPV1) receptors. Mainly under acidic conditions, it is transformed to the cyclooxygenase inhibitor oxaprozin, which is ineffective for neuropathy. Therefore, an enterosolvent capsule is suggested for oral formulation, which we investigated for nociception, basic kinetics, and thermoregulatory safety in mice. The antihyperalgesic effect of SZV 1287 (10, 20, 50, and 200 mg/kg, p.o.) was determined in partial sciatic nerve ligation-induced traumatic neuropathy by aesthesiometry, brain and plasma concentrations by HPLC, and deep body temperature by thermometry. Its effect on proton-induced TRPV1 activation involved in thermoregulation was assessed by microfluorimetry in cultured trigeminal neurons. The three higher SZV 1287 doses significantly, but not dose-dependently, reduced neuropathic hyperalgesia by 50% of its maximal effect. It was quickly absorbed; plasma concentration was stable for 2 h, and it entered into the brain. Although SZV 1287 significantly decreased the proton-induced TRPV1-mediated calcium-influx potentially leading to hyperthermia, it did not alter deep body temperature. Oral SZV 1287 inhibited neuropathic hyperalgesia and, despite TRPV1 antagonistic action and brain penetration, it did not influence thermoregulation, which makes it a promising analgesic candidate.

2002 ◽  
Vol 16 (4) ◽  
pp. 354-357 ◽  
Author(s):  
Michiaki Yamakage ◽  
Sohshi Iwasaki ◽  
Akiyoshi Namiki

1992 ◽  
Vol 26 (3) ◽  
pp. 191-198 ◽  
Author(s):  
Kazushi Daimon ◽  
Naoto Yamada ◽  
Tetsushi Tsujimoto ◽  
Saburo Takahashi

1987 ◽  
Vol 39 (3) ◽  
pp. 367-370 ◽  
Author(s):  
Mark S. Blumberg ◽  
Julie A. Mennella ◽  
Howard Moltz

1992 ◽  
Vol 163 (1) ◽  
pp. 139-151 ◽  
Author(s):  
R. M. BEVAN ◽  
P. J. BUTLER

Six tufted ducks were trained to dive for food at summer temperatures (air, 26°C, water, 23°C) and at winter temperatures (air, 5.8°C, water 7.4°C). The mean resting oxygen consumption (Voo2) a t winter temperatures (rwin) was 90% higher than that at summer temperatures (Tsum), but deep body temperatures (Tb) were not significantly different. Diving behaviour and mean oxygen consumption for dives of mean duration were similar at Twin and at Tsum, although the mean oxygen consumption for surface intervals of mean duration was 50% greater at Twin and Tb was significantly lower (1°C) at the end of a series of dives in winter than it was in summer. There appears to be an energy saving of 67 J per dive during winter conditions and this may, at least partially, be the result of the metabolic heat produced by the active muscles being used to maintain body temperature. While at rest under winter conditions, this would be achieved by shivering thermogenesis. Thus, the energetic costs of foraging in tufted ducks in winter are not as great as might be expected from the almost doubling of metabolic rate in resting birds.


1965 ◽  
Vol 20 (4) ◽  
pp. 737-741 ◽  
Author(s):  
Frederick M. Hart ◽  
J. Job Faber

The differences between fetal deep body temperature and maternal aortic temperature were measured in 10 New Zealand white rabbits of 22—29 days gestation with thermocouples thrust into the fetuses immediately after the animals had been killed by a warmed overdose of sodium pentobarbital. Fetal temperatures exceeded maternal temperatures by —2.51 + 0.099.X °C, where X is the gestational age in days. There is 95% confidence that fetal temperatures exceeded maternal temperature by at least 0.25 °C at a fetal age of 29 days. Permanently implanted thermocouples in six nonpregnant rabbits showed that the ventral surface of the abdominal cavity is colder than the aorta, and that the dorsal surface is slightly warmer. Fetal heat loss is partly via the umbilical circulation and partly via the fetal body surface. tissue temperatures in rabbits; fetal heat loss Submitted on September 28, 1964


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