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Biomedical subjects

W L Dewey

Publications and source records attributed to W L Dewey.

At least 19 recordsLinked to original sources
PubMed1979

Optically pure (+)-nicotine from (+/-)-nicotine and biological comparisons with (-)-nicotine.

Optically pure (+)-nicotine has been obtained from (+/-)-nicotine using a combination of d-tartaric acid and di-p-toluoyl-l-tartaric acid. As the di-d-tartrate salt, (+)-nicotine is less potent than (-)-nicotine di-l-tartrate in producing lethality in mice, on blood pressure in anesthetized rats, and in the isolated guinea-pig ileum, indicating substantial stereospecificity for nicotine receptors. Potency ratios are 0.14, 0.06, and 0.019, respectively.

Animals↗
PubMed1979

Some 11-substituted tetrahydrocannabinols. Synthesis and comparison with the potent cannabinoid metabolites 11-hydroxytetrahydrocannabinols.

A series of compounds was prepared in which the 11-hydroxyl of 11-hydroxy-delta8-THC, the potent metabolite of delta8-THC, was replaced by a methyl, methyoxy, amino, or acetamido group. All of the compounds tested produced behavioral changes in dogs, but only the methoxy compound has analgesic properties in mice. An isosteric oxime was inactive in mice.

Analgesics↗
PubMed1979

Some 9-hydroxycannabinoid-like compounds. Synthesis and evaluation of analgesic and behavioral properties.

A series of 9-hydroxylated cannabinoid-like compounds was prepared and tested for analgesic properties in mice and behavioral properties in dogs. Although the prototype compound, 9-nor-9-hydroxyhexahydrocannabinol, has potent antinociceptive activity in laboratory animals, the new analogues were relatively inactive. All of the compounds produced an alteration of behavior in unanesthetized dogs. Two of the compounds produced cannabinoid-like effects and the other two produced general CNS depression.

Analgesics↗
PubMed1978

A comparison of some pharmacological actions of morphine and delta9-tetrahydrocannabinol in the mouse.

The effects of morphine and delta9-tetrahydrocannabinol(THC)on the tail-flick reflex, body temperature, and catecholamine synthesis were examined in the mouse in order to compare their effects in a single species and strain under uniform conditions. Naloxone antagonism of THC and cross-tolerance between morphine and THC were also studied. Both morphine and THC produced antinociception, hypothermia, and increased catecholamine synthesis at 30 min after s.c. injection. Morphine produced greater increases in dopamine synthesis and was a more potent antinociceptive agent, while THC produced greater increases in norepinephrine synthesis and was a more potent hypothermic agent. Naloxone pretreatment (1 mg/kg) partially antagonized the hypothermia and increase in catecholamine synthesis produced by THC. There was also cross-tolerance between morphine and THC, but it was asymmetric in that THC-tolerant animals were cross-tolerant to only the hypothermic action of morphine and morphine-tolerant animals cross-tolerant to only the antinociceptive action of THC.

Analgesics↗
PubMed1978

Cannabinoid effects on plasma corticosterone and uptake of 3H-corticosterone by mouse brain.

The effects of three cannabinoids, 11-hydroxy-delta9-tetrahydrocannabinol (11-HO-delta9-THC), delta9-THC and cannabinol (CBN), ranging in behavioral activity from high to low, were studied on two aspects of pituitary--adrenal function. Plasma corticosterone levels were used as an index of adrenocorticotropic hormone (ACTH) release. All three cannabinoids elicited an increase in plasma corticosterone elvels in a manner similar to their behavioral potency. These cannabinoids also elicited an increase in the concentration of 3H-corticosterone taken up by the brains of adrenalectomized mice in a manner similar to their potency in elevating plasma corticosterone levels. The significance and possible underlying mechanism of the apparent correlation resulting between these effects and the behavioral effects of cannabinoids are discussed.

Adrenalectomy↗
PubMed1978

Possible effects of normetabolites on the subjective and reinforcing characteristics of opioids in animals and man.

When an opioid capable of forming active metabolites is administered, the total pharmacology is the result of interactions of the opioid and such metabolites, especially normetabolites. Normetabolites may affect the morphine-like characteristics of certain opioids and thus influence their reinforcement in animals and man. Most opioids, when administered in single doses, are positively reinforcing in addicts. Oral administration, as compared with parenteral, facilitates the formation of normetabolites. When chronically administered, many opioids, including acetylmethadol, meperidine, morphine, codeine, propoxyphene, and levorphanol, show evidence of a longer half-life for their normetabolites. Normetabolites may have aversive characteristics and thus impair positive reinforcement of the parent drug in animals and man. For example, addicts do not like chronic oral morphine or chronic oral codeine. Conversely, methadone, the normetabolites of which are inactive, is well accepted during chronic oral administration. Drugs which inhibit N-demethylation will increase the agonist potency of opioids having inactive normetabolites (e.g., methadone) but will decrease the agonist potency of opioids having more potent normetabolites than the parent (e.g., acetylmethadol). The divergent responses of addicts to single doses of opiates as compared with chronic doses indicate that chronic addiction tests in man are needed befored relative abuse liability can be predicted.

Animals↗
PubMed1978

Effects of delta9-THC on the synaptosomal uptake of 3H-tryptophan and 3H-choline.

The in vitro addition of (-)-delta9-tetrahydrocannabinol (delta9-THC) resulted in a dose-responsive inhibition of the high-affinity specific synaptosomal uptake of both 3H-tryptophan and 3H-choline in mouse forebrain crude synaptosomal preparations. The approximate concentrations of delta9-THC required to cause a 50% inhibition of the uptake of 3H-tryptophan and 3H-choline were 33 and 16 muM, respectively. Kinetic analysis showed that inhibition of both compounds were consistent with a noncompetitive mechanism. The pretreatment of mice with doses of 10, 30 or 100 mg/kg delta9-THC had no effect on the subsequent in vitro synaptosomal uptake of either 3H-tryptophan or 3H-choline into forebrain synaptosomes.

Animals↗
PubMed1978

Effects of divalent cations, lanthanum, cation chelators and an ionophore on acetylcholine antinociception.

The antinociceptive effect of intracerebroventricularly administered acetylcholine as measured in the mouse tail-flick test was reduced by intracerebroventricularly injected calcium, magnesium and manganese. Maximum antagonism of acetylcholine-induced antinociception was observed with a 1-hour calcium pretreatment. Significant reduction existed at 2- but not 4-hour pretreatment. Barium and strontium were inactive. The antinociceptive effect of acetylcholine was potentiated by lanthanum and ethylene glycol tetraacetic acid but not by ethylenediamine tetraacetic acid. The ionophore A23187 was shown to increase greatly the antagonistic effect of a low dose of calcium. The ionophore alone did not significantly alter the effect of acetylcholine. Thus, it appears that calcium must penetrate cell membranes to reduce the effect of acetylcholine. In addition to acetylcholine, it was found that the antinociceptive effects of oxotremorine and physostigmine could also be reduced by calcium. These data indicate that alterations in intracellular calcium are involved in cholinergically induced antinociception.

Acetylcholine↗