thebaine and Pain

The search for selective kappa opioid receptor (κOR) agonists with an improved safety profile is an area of interest in opioid research. In this work, a series of

Topics: Analgesics, Opioid; Animals; CHO Cells; Cricetulus; Hot Temperature; Humans; Male; Mice; Molecular Docking Simulation; Pain; Rats, Sprague-Dawley; Receptors, Opioid, kappa; Thebaine

In this study, we synthesized some novel N-(tetrazol-1H-5-yl)-6,14-endoethenotetrahydrothebaine 7α-substituted 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives as potential analgesic agents. The structures of the compounds were established on the basis of their IR, ¹H NMR, ¹³C NMR, 2D NMR, and high-resolution mass spectral data. The analgesic activity was evaluated by a rat-hot plate test model and a rat tail-flick model. Compound 12 showed analgesic activity higher than that of morphine. In addition to a histopathological and biochemical evaluation, the LD₅₀ dose for the most active compound 12 was determined.

Topics: Analgesics; Animals; Disease Models, Animal; Lethal Dose 50; Magnetic Resonance Spectroscopy; Male; Morphine; Oxadiazoles; Pain; Rats; Rats, Wistar; Thebaine; Thiadiazoles

The analgesic activity of oripavine and phi-dihydrothebaine (5, 6, 8, 14-tetrahydro-4-hydroxy-3, 6-dimethoxy-17-methylmorphinan) has been studied in the mouse and rat with the hot-plate technique after s.c. drug administration. Peak analgesic effects in the mouse and rat were observed 20 min following drug administration, and the effect lasted about 40 to 60 min. Median analgesic (AD50) and lethal (LD50) doses and 95% confidence limits are presented. Oripavine and phi-dihydrothebaine appear to have analgesic potency of the same order as morphine in these species but have low therapeutic indexes because of severe toxicity. Toxic signs of oripavine and phi-dihydrothebaine in both species were clonic-tonic convulsions followed by death. The toxicity of oripavine, phi-dihydrothebaine and morphine in the mouse did not appear to be antagonized by pretreatment with 1 mg/kg of naloxone given 10 min prior to the test drug. toxicity does not appear to be mediated at the opiate receptor; however, oripavine did show some cross tolerance with morphine, but did not appear to suppress morphine abstinence in the mouse and rat.

Topics: Analgesics, Opioid; Animals; Drug Tolerance; Lethal Dose 50; Male; Mice; Mice, Inbred ICR; Morphine; Naloxone; Pain; Rats; Rats, Inbred Strains; Thebaine

The effects of various narcotic analgesics on striatal homovanillic acid (HVA) content, hot plate time and rectal temperature in mice were compared in relation to dose and time. The hypothermia induced by narcotic analgesics did not correlate with the striat"al HVA increase. Pentazocine, cyclazocine and thebaine had no effect on the hot plate time. The maximum prolongation of hot plate time induced by morphine, methadone or piminodine occurred before the highest HVA increase. The highest increase induced by narcotic analgesics in striatal HVA content was twice the original concentration. This occurred 2 hr after 40 mg/kg of morphine; 2 hr after 20 mg/kg of methadone; 1/2 hr after 20 mg/kg of piminodine; and 1 hr after 60 mg/kg of pentazocine. Cyclacozine (10 and 20 mg/kg) and thebaine (10 mg/kg) did not alter the HVA content. With the exception of pentazocine, those doses of narcotic analgesics that caused equal increases in striatal HVA content were also equianalgesic. These results suggest that there are similarities in the structural requirements for antinociceptive and striatal HVA-increasing effects of narcotic analgesics. The neuroleptic compound haloperidol (0.5 mg/kg) caused a fourfold increase in striatal HVA content making it twice as efficient as narcotic analgesics. This finding suggests that narcotic analgesics do not act on the same sites as neuroleptics when causing an increase in striatal HVA content.

Topics: Analgesics, Opioid; Animals; Body Temperature; Corpus Striatum; Cyclazocine; Haloperidol; Homovanillic Acid; Male; Methadone; Mice; Morphine; Pain; Pentazocine; Phenylacetates; Piperidines; Thebaine; Time Factors