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PubMed2003

Involvement of the kappa-opioid receptor in the anxiogenic-like effect of CP 55,940 in male rats.

We have studied the possible interaction between three selective opioid-receptor antagonists, nor-binaltorphimine (NB: kappa) (5 mg/kg), cyprodime (CY: mu) (10 mg/kg) and naltrindole (NTI: delta) (1 mg/kg), and the cannabinoid receptor agonist CP 55,940, in the modulation of anxiety (plus-maze) and adrenocortical activity (serum corticosterone levels by radioimmunoassay) in male rats. The holeboard was used to evaluate motor activity and directed exploration. CP 55,940 (75 microg/kg, but not 10 microg/kg) induced an anxiogenic-like effect, which was antagonised by NB. The other effects of CP 55,940 (75 microg/kg), a decreased holeboard activity and stimulation of adrenocortical activity, were not antagonised by any of the three opioid receptor antagonists. CY and NTI, when administered alone, induced marked reductions in motor activity, anxiogenic-like effects and stimulation of adrenocortical activity. The selective kappa-opioid receptor antagonist NB, on its own, did not modify the level of anxiety but stimulated adrenocortical activity. We provide the first pharmacological evidence about the involvement of the kappa-opioid receptor in the anxiogenic-like effect of CP 55,940.

Animals↗
PubMedDate not supplied

The selective cannabinoid antagonist SR 141716A blocks cannabinoid-induced antinociception in rats.

The purported CB1 cannabinoid antagonist SR 141716A has proven to be a useful tool in the investigation of cannabinoid pharmacology. This antagonist was employed in the present study to investigate the antinociceptive and cataleptic effects of cannabinoids after either systemic or intracerebroventricular (ICV) administration. The antinociceptive potency of systemically administered delta 9-tetrahydrocannabinol (delta 9-THC) was decreased 18-fold by SR 141716A, from an ED50 value of 0.3-5.1 mg/kg. Similarly, it completely blocked the antinociceptive effects of delta 9-THC and CP 55,940, a potent bicyclic cannabinoid, after ICV administration. In addition, it prevented cannabinoid-induced catalepsy when given by either route of administration. In contrast, SR 141716A failed to antagonize the antinociceptive effects of morphine, indicating its selectivity for cannabinoid receptors. These findings indicate that the antinociceptive and cataleptic effects of delta 9-THC and CP 55,940 are mediated through CB1 cannabinoid receptors.

Analgesics↗
PubMed1997

Changes in rat spleen cannabinoid receptors after chronic CP-55,940: an autoradiographic study.

We examined whether cannabinoid receptor density changes in the rat spleen after in vivo chronic exposure to cannabinoids. Rats received daily injections of 0.4 mg/kg IP of the synthetic cannabinoid receptor ligand CP-55,940 for 11 days. One h after the last injection on day 11, the rats were killed and spleen coronal sections were processed for receptor binding autoradiography with 10 nM of [3H]CP-55,940 in the absence or presence of unlabeled CP-55,940 (10 microM). Densitometric analysis of the autoradiograms showed significant loss of [3H]CP-55,940 binding of about 42% in chronic cannabinoid-treated, tolerant rats. Our findings indicate that cannabinoid receptors basically present in immune spleen cells are down-regulated by chronic exposure to cannabinoids, suggesting a role in immune modulation and in the impairment of immune function.

Animals↗
PubMed1999

Thujone exhibits low affinity for cannabinoid receptors but fails to evoke cannabimimetic responses.

Absinthe, an abused drug in the early 1900s, has been speculated to activate the receptors responsible for marijuana intoxication (the CB1 cannabinoid receptor) (Nature 253:365-356; 1975). To test this hypothesis, we investigated oil of wormwood (Artemisia absinthium) the active plant product found in absinthe, and thujone, the active compound found in oil of wormwood. Radioligand receptor binding assays employing membrane preparations from rat brains containing CB1 cannabinoid receptors, and human tonsils containing CB2 receptors, demonstrated that thujone displaced [3H]CP55940, a cannabinoid agonist, only at concentrations above 10 microM. HPLC analysis of oil of wormwood revealed that only the fractions having mobility close to thujone displaced [3H]CP55940 from the CB1 cannabinoid receptor. [35S]GTPgammaS binding assays revealed that thujone failed to stimulate G-proteins even at 0.1 mM. Thujone failed to inhibit forskolin-stimulated adenylate cyclase activity in N18TG2 membranes at 1 mM. Rats administered thujone exhibited different behavioral characteristics compared with rats administered a potent cannabinoid agonist, levonantradol. Therefore, the hypothesis that activation of cannabinoid receptors is responsible for the intoxicating effects of thujone is not supported by the present data.

Adenylyl Cyclase Inhibitors↗
PubMed2000

Effect of subchronic antidepressant treatments on behavioral, neurochemical, and endocrine changes in the forced-swim test.

The purpose of the present study was to examine the effect of subchronic treatment (24 days) with antidepressants displaying differential effects on noradrenaline and serotonin reuptake, on behavior, neurochemistry, and hypothalamic-pituitary-adrenal (HPA) axis activity following FST exposure in the rat. Desipramine (7.5 mg/kg, IP) significantly decreased immobility in the FST, whilst paroxetine (7.5 mg/kg IP) and venlafaxine (10 mg/kg, IP) were without effect. Nonetheless, treatment with all three antidepressants significantly attenuated stress-related increases in amygdaloid and cortical serotonin turnover. Of the three antidepressants examined, only desipramine attenuated the stress-associated elevation in serum corticosterone. In conclusion, although FST-induced increases in serotonin turnover in the frontal cortex and amygdala were attenuated following treatment with all three antidepressants, FST-induced behavioral changes and increased HPA axis activity were normalized only following desipramine treatment. In addition, these results suggest that neurochemical mechanisms independent of increased serotonergic activity subserve the normalization of behavior and HPA axis responses in the FST. These data also add to our understanding of the interactions between antidepressants and stress-induced behavioral, neurochemical, and endocrine alterations, and illustrates important differences between classes of antidepressants.

Amygdala↗
PubMed1993

Retrievability of Thermafil plastic cores using organic solvents.

Twenty distal roots of extracted mandibular first and second molars were instrumented, then obturated using Thermafil obturating material with solid plastic core carriers. To simulate a retreatment process, the gutta-percha was softened using one of four solvents, chloroform, xylene, eucalyptol, or halothane. A K file was used to advance the solvent into the gutta-percha and to engage the plastic carrier. In all but one case, the plastic carriers were easily removed from the root canal. It was concluded that the plastic carriers used with the Thermafil obturation media do not present a difficult obstacle for removal should the root require retreatment.

Chloroform↗
PubMed1991

Halothane and eucalyptol as alternatives to chloroform for softening gutta-percha.

Because chloroform was identified as a potential carcinogen by the Food and Drug Administration, interest has been revived to identify an alternative solvent to soften gutta-percha for removal from obturated root canals. This study compared the effectiveness of halothane, eucalyptol, and chloroform in softening gutta-percha in simulated root canals. One milliliter of a solvent was placed into a small glass funnel whose stem was obturated with a 30-mm column of gutta-percha. After 30 s, softening was evaluated for each solvent by recording the time required to reach a depth of 10 mm by hand filing with a #100 Hedstrom file. The depth of penetration of a #40 finger plugger under constant weight for 15 min was also determined for each solvent. By using a one-way analysis of variance and Scheffe's test, all comparisons were not significant except for the depth of penetration with constant weight between chloroform and halothane (p less than 0.05). The results indicate that halothane and eucalyptol are suitable alternatives to chloroform as gutta-percha softening solvents.

Analysis of Variance↗
PubMed1990

Evaluation of Gutta-percha solvents.

Five solvents (rectified white turpentine, oil of melaleuca, eucalyptol, white pine oil, and pine needle oil) were compared with chloroform for their ability to dissolve gutta-percha. All solvents dissolved at least 50% of the gutta-percha in 15 min at 37 degrees C with chloroform and rectified white turpentine dissolving the gutta-percha completely.

Chloroform↗
PubMed1989

A comparison of four root canal filling techniques.

This study compared the apical seal produced by four obturation techniques. Sixty-four extracted human teeth were prepared and obturated using lateral condensation of gutta-percha that was either unmodified or was dipped in chloroform, eucalyptol, or eucapercha paste. After storage in normal saline and 0.02% azide solution at 37 degrees C for 200 days, the teeth were immersed in India ink for 48 h. The most coronal extent of leakage of India ink into the canal was then determined. Significantly more apical leakage occurred in the eucapercha group than in the other three groups. All other comparisons were equivalent. The results suggest that modification of the gutta-percha master cone with solvent does not improve the apical seal in vitro. If modification is desired, then dipping the master cone in either eucalyptol or chloroform produces an apical seal superior to that achieved with eucapercha.

Chloroform↗
PubMed1989

A comparison of apical seal: chloroform versus eucalyptol-dipped gutta-percha obturation.

Three groups of extracted teeth were obturated using gutta-percha and lateral condensation. In one group the gutta-percha was dipped in chloroform before condensation. In a second a eucalyptol dip was used. No dip was used in the third group. A dye penetration study was done to compare leakage among the three groups. The teeth were cleared for viewing and measurements of dye penetration were made using a stereomicroscope. Statistical analysis using Kruskal-Wallis one-way analysis of variance of the results showed no significant difference among test groups at the 0.05 level.

Chloroform↗
PubMed1997

Effectiveness of eucalyptol and d-limonene as gutta-percha solvents.

Eucalyptol and d-limonene were evaluated for their ability to serve as a substitute solvent for chloroform. The amount of time required to soften and remove the gutta-percha in 72 instrumented and filled simulated root canals in epoxy blocks was measured. After preparation to the apices of the block canals with a #60 file, four different filling techniques were used. These obturations were softened with each solvent and then removed, first using a #15 Hedstrom file inserted to full working length, and then removing the remaining filling mass with a #60 reamer. The two instrument placements were timed: one for the Hedstrom file insertion to the apex and the other for the reamer to remove the filling material. Neither the different solvents nor the filling techniques had a significant effect on the times required for the H-files to reach the apex. However, the times for the reamer to remove the filling materials were effected both by the filling techniques and the solvents used.

Chloroform↗
PubMed2000

Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial.

BACKGROUND: Hot flashes can be troublesome, especially when hormonal therapy is contraindicated. Preliminary data have suggested that newer antidepressants, such as venlafaxine, can diminish hot flashes. We undertook a double-blind, placebo-controlled, randomised trial to assess the efficacy of venlafaxine in women with a history of breast cancer or reluctance to take hormonal treatment because of fear of breast cancer. METHODS: Participants were assigned placebo (n=56) or venlafaxine 37.5 mg daily (n=56), 75 mg daily (n=55), or 150 mg daily (n=54). After a baseline assessment week, patients took the study medication for 4 weeks. All venlafaxine treatment started at 37.5 mg daily and gradually increased in the 75 mg and 150 mg groups. Patients completed daily hot-flash questionnaire diaries. The primary endpoint was average daily hot-flash activity (number of flashes and a score combining number and severity). Analyses were based on the women who provided data throughout the baseline and study weeks. FINDINGS: 191 patients had evaluable data for the whole study period (50 placebo, 49 venlafaxine 37.5 mg, 43 venlafaxine 75 mg, 49 venlafaxine 150 mg). After week 4 of treatment, median hot flash scores were reduced from baseline by 27% (95% CI 11-34), 37% (26-54), 61% (50-68), and 61% (48-75) in the four groups. Frequencies of some side-effects (mouth dryness, decreased appetite, nausea, and constipation) were significantly higher in the venlafaxine 75 mg and 150 mg groups than in the placebo group. INTERPRETATION: Venlafaxine is an effective non-hormonal treatment for hot flashes, though the efficacy must be balanced against the drug's side-effects. Confirmation of the results of this 4-week study awaits the completion of three ongoing randomised studies to assess the effects of other related antidepressants for the treatment of hot flashes.

Antidepressive Agents, Second-Generation↗
PubMed1979

A glycoside-hydrolase inhibitor in treatment of dumping syndrome.

BAY g 5421, a glycoside-hydrolase inhibitor, produced symptomatic improvement in ten patients with the dumping syndrome. 100 mg BAY g 5421, given before a 50 g sucrose meal, produced pronounced attenuation of both hyperglycaemic and hypoglycaemic phases of plasma glucose levels; and it greatly reduced the rise in plasma levels of gastric inhibitory polypeptide and insulin. Gastric emptying, studied simultaneously by an isotopic method, showed little difference between tests, suggesting that the improvement achieved was not mediated by slowing gastric emptying.

Adult↗