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Biomedical subjects

T C Spaulding

Publications and source records attributed to T C Spaulding.

7 recordsLinked to original sources
PubMed1979

Antinociceptive activity of clonidine and its potentiation of morphine analgesia.

The activity of clonidine and its interaction with morphine was assessed in the mouse tail flick assay. In this assay, clonidine was found to be 10 times more potent than morphine. Clonidine potentiated morphine antinociceptive activity approximately five-fold and morphine potentiated clonidine activity four-fold. Clonidine's agonstic activity was not reversed by naloxone hydrochloride (10 mg/kg) while the potentiating effect of clonidine by morphine was. Tolerance to the antinociceptive effect of morphine was observed in morphine pellet-implanted mice but no cross tolerance was observed for clonidine. These data indicate that clonidine-induced analgesia is not a result of an interaction at morphine receptors; but rather, common pathway(s) are present which appear to complement the agonistic interaction of each.

Analgesics↗
PubMed1979

Synthesis and analgesic activity of some spiro[dibenz[b,f]oxepin-10,4'-piperidine] derivatives.

A series of 10,11-dihydro-11-oxospiro[dibenz[b,f]oxepin-10,4'-piperdine] derivatives (II) was synthesized and evaluated for analgesic activity in the phenylquinone writhing assay (PQW) and the tail-flick test in mice. Preliminary structure-activity correlations indicate that optimum activity is associated with a short-chain (R less than or equal to C2) N substituent and a nuclear fluorine function, as exemplified by 9b. This compound, when administered orally, was equipotent to morphine in protecting against mouse writhing. The observation that the PQW activity of 9b remained relatively unchanged after naloxone challenge seems to favor a nonnarcotic profile.

Analgesics↗
PubMed1975

Relationship of brain morphine levels to analgesic activity in acutely treated mice and rats and in pellet implanted mice.

The relationship of brain morphine concentration, determined fluorometrically, to tail-flick activity was investigated after acute and chronic morphine treatment of mice and acute treatment of rats. Brain morphine levels were quantitatively related to the analgesic effect on acute administration, with levels of 100 and 140 ng/g of tissue corresponding to the ED50 in mice and rats, respectively. Over a 90-minute time course after acute s.c. injection, the analgesic effect of morphine in the tail-flick test lagged slightly behind morphine brain level in both species. In mice implanted s.c. with morphine pellets, significant analgesia and appreciable morphine brain levels appeared as early as 20 to 30 minutes after implantation. Increased brain morphine corresponded to increased analgesia at 1 and 4 hours after implantation. Tolerance was evident by 24 hours after implantation and was maximal at 72 hours. Brain morphine remained elevated up to 144 hours after implantation even though substantial encapsulation of the pellet occurred within 72 hours. If pellets were removed at 72 hours, brain morphine declined to control levels with 6 hours, but significant tolerance persisted for at least 24 hours after pellet removal. These results demonstrate that morphine is absorbed from the pellet up to 6 days after implantation and that the decreased analgesic activity observed in the latter times is due to tolerance to the narcotic and not to a decrease in absorption from the pellet.

Analgesics↗
PubMedDate not supplied

Microsomal spectral properties and narcotic N-demethylase activity in methadone-dependent rats.

Rats were given access ad lib. to various concentrations (0.3 to 1.0 mg/ml) of methadone hydrochloride dissolved in sucrose solution. The N-demethylation of various narcotics was studied in hepatic preparations from methadone-consuming rats in order to determine if there was substrate specificity for the microsomal demethylase system. The Vmax for the N-demethylation of methadone, ethylmorphine, and meperidine was increased by 40-65%, whereas that for morphine N-demethylation was reduced to 55% of the control value. Additive or synergistic effects on microsomal cytochrome P-450 content were seen when methadone consumption was supplemented by administration of maximally inducing doses of either 3-methylcholanthrene (3-MC) or phenobarbital (PB). This suggested that there was an increase in a type of cytochrome P-450 which was independent of that induced by PB or 3-MC. The qualitative change in cytochrome P-450 reflected in the ethylisocyanide binding spectrum was also apparent after treatment with methadone, PB, or 3-MC, and the combination of methadone and PB exhibited effects that differed from PB alone. Two-substrate kinetic analysis with methadone and morphine as substrates indicated that more than one enzymic system may be involved in the N-demethylation reaction and that a common component of this N-demethylase system could not be induced with phenobarbital. However, methadone and meperidine seem to be demethylated by the same enzymic system.

Animals↗