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P D Thut

Publications and source records attributed to P D Thut.

17 recordsLinked to original sources
PubMed1995

A rabbit tooth-pulp assay to quantify efficacy and duration of antinociception by local anesthetics infiltrated into maxillary tissues.

The rabbit tooth-pulp assay is well established as a method for measuring the efficacy and potency of parenteral analgesic drugs. We describe a method for administration of local anesthetic drugs into the maxillary arch and subsequent measurements of antinociceptive action. It was possible to use two different methods of ED50 estimation and to provide measures of the potency, efficacy, and duration of local anesthetic drugs. These measurements corresponded with in vitro estimates of potency and duration and with intrinsic observations of the clinical actions.

Analgesia↗
PubMed1993

The effects of different antiemetic agents on morphine-induced emesis in ferrets.

There is interest in the development of antiemetics other than dopamine receptor antagonists for the treatment of postoperative nausea and vomiting. A ferret model of morphine-induced emesis may have wider application in evaluating newer agents than the apomorphine dog model. This study describes the conditions for morphine-induced emesis in ferrets and evaluates five antiemetics that are prototypical of three different mechanisms. The average numbers of vomiting and retching episodes induced by morphine (0.1-2.5 mg/kg s.c.) were distributed as a bell-shaped curve. Maximum number of vomits occurred at 0.3 mg/kg (11.8 +/- 2.1 vomits; 45 +/- 12.5 retches). Antiemetics or vehicle were given i.v. 5 min prior to morphine while each ferret was maintained under isoflurane-O2 anesthesia. Ondansetron, a 5-HT3 receptor antagonist, reduced vomiting episodes by 47% and 70% (3 and 10 mg/kg). Granisetron, a 5-HT3 receptor antagonist was inactive at doses of 0.1, 1.0, 3.0 and 10 mg/kg. Metoclopramide reduced vomiting episodes by 48% and 82% (3 and 10 mg/kg). Droperidol reduced vomiting episodes by 84% at 3 mg/kg. Naloxone reduced vomiting episodes by 91% and 43% at doses of 0.1 and 1.0 mg/kg. In most cases, prolonged latency times to the first episodes accompanied the reduction in total numbers of episodes. The significant reduction of morphine-induced emesis in the ferret by ondansetron, metoclopramide and droperidol is consistent with the reduction of postoperative emesis in man by these compounds when morphine was a component of the anesthetic regimen. These results suggested that the morphine ferret model may be useful for evaluating compounds having the potential for preventing and treating postoperative vomiting.

Anesthesia↗
PubMed1991

Imipramine-fentanyl antinociception in a rabbit tooth pulp model.

Antinociception of imipramine (I) and its effect in combination with fentanyl (F) was evaluated in rabbits using electrically-induced lick chew responses via tooth pulp stimulation as the model of nociception. Acute i.v. injections of I elicited a graded dose response comparable to i.v. morphine (M) with I ED 50 = 4.35 mg/kg (2.31-8.14, 95% CL) and M ED 50 = 1.81 mg/kg (1.11-3.90), with no differences in the slopes between the two curves. The lethal dose of I was 10 mg/kg. An i.v. dose of I twice the ED 50 elicited an antinociceptive effect of more than 50% maximum possible effect (MPE) for 90 minutes with peak effect of 82% MPE occurring at 15 minutes. These effects of I were not reversed by a morphine-reversal dose of naloxone (0.1 mg/kg i.v.) but were reversed with a ten fold dose of naloxone. F ED 50 values (mcg/kg) were lowered from 11.35 to 2.70, 0.74 and 0.33 with increasing pretreatment doses of I (1.0, 2.1 and 3.2 mg/kg). These magnitudes of potency increases of F were 4.2, 15.3 and 34.4 fold respectively. A single i.v. ED 50 dose of I extended the time to 50% MPE of an ED 90 dose of F from 26 minutes to 77 minutes; of a 2 X ED 50 dose of F from 17 minutes to 28 minutes. Data points for three different combinations of I and F fell significantly within the synergistic field of an ED 50 isobologram and a polynomial equation described the curve best fitting the data points. F alone (i.v. ED 50 dose) increased the PaCO2 values to 74% above controls and three different combinations with I showed no increases in PaCO2 values above controls. I alone did not significantly cause any change in PaCO2 values from controls.

Analgesics↗
PubMed1984

A rabbit tooth-pulp assay to determine ED50 values and duration of action of analgesics.

The rabbit tooth-pulp assay is well established as a standard and reliable method to test for analgesic activity of drugs. Traditional methods to compare potencies of narcotic analgesics have been to establish ED50 values from rodent hot-plate and tail-flick tests. We describe a modification of the tooth-pulp assay with the use of a microcomputer to generate ED50 values based on "all or none" quantal responses and to evaluate durations of action, with the use of relatively few animals to test several drugs. The potencies of morphine, fentanyl, and alfentanil were established and compared to those from the mouse hot-plate assay. The rank order of potencies were the same and the absolute values were consistently lower. The ED50 value of pentazocine was determined with the tooth-pulp assay but could not be determined with the standard mouse hot-plate assay. The assay provides an additional, reliable, and sensitive method to generate ED50 values and to evaluate durations of action of narcotic analgesics.

Alfentanil↗
PubMed1984

Development of new agents and techniques for intravenous analgesia.

The search for new anesthetic and analgesic drugs will be aided by analysis of the structures of chemical compounds which variously stimulate the five proposed opioid receptors or the benzodiazepine receptors. The mechanism of interaction between the benzodiazepines, opioids, and the neuroleptics will be further elucidated. These studies will result in discovery of drugs with fewer side-effects and more specific clinical effects.

Analgesics, Opioid↗
PubMedDate not supplied

Suppression of conditioned drinking by taurine and related compounds.

Mice were conditioned to respond for water reinforcements on a FR-5 schedule. Taurine, injected intraperitoneally at doses of 9.0, 13.8, and 21.3 mmole/kg 30 min prior to the experimental session, produced a dose-related decrease in both the initial response rate and total number of reinforcements received by mice deprived of water for 24 hr. The structural analogues of taurine (aminomethanesulfonic acid, 3-aminopropanesulfonic acid, beta-alanine, cysteamine, and glycine) also produced a hypodipsia. Doses of taurine which produced depression of responding for water reinforcements were used which produced no suppression of spontaneous motor activity, rotarod performance, Sidman avoidance, or shuttle-box avoidance. After intraperitoneal injection, the concentration of taurine increased in the hypothalamus and medulla, but not in other brain areas. We suggest that taurine might be acting by specifically depressing areas of the hypothalamus which stimulate drinking.

Animals↗
PubMedDate not supplied

Hemodynamic changes during isoflurane anesthesia.

Isoflurane is known to produce slight tachycardia in humans. This study examined the effects of isoflurane on cardiovascular parameters in dogs. Four groups, with six dogs per group, were anesthetized with isoflurane. Prior to isoflurane administration, a femoral artery catheter was inserted. Group 1 was anesthetized with isoflurane alone. Group 2 was pretreated with fentanyl prior to administration of isoflurane. Group 3, anesthetized with isoflurane alone, had a Swan-Ganz catheter introduced through the external jugular vein. Group 4 was pre-treated with fentanyl prior to administration of isoflurane, and had a Swan-Ganz catheter. Physiologic parameters were recorded at 15-min intervals as isoflurane was reduced from 3.5% to 1.5% by 0.5% increments. Heart rate increased while blood pressure decreased during induction (8.5 min) in Group 1 and then returned to control values. In Group 2, heart rate declined with no changes in blood pressure over all isoflurane concentrations. The induction time (time from initiation of the anesthetic until intubation was achieved) was 2 min. In Group 3, the heart rate increased and the blood pressure decreased, with an induction time of 10 min. Cardiac output and pulmonary artery pressure varied inversely to the isoflurane concentration. In Group 4, heart rate decreased with a minimal decrease in blood pressure, and an induction time of 3.5 min. Cardiac output and pulmonary artery pressure varied inversely to the isoflurane concentration. A fifth group of 6 dogs was monitored for heart rate only, while a mask was placed over their noses to simulate the procedure for the administration of an anesthetic. The heart rate increased similar to that of the dogs in Groups 1 and 3, but the tachycardia was abolished with the administration of fentanyl. Increased heart rate could not be directly attributed to isoflurane but was probably due to catecholamines released during induction. Fentanyl blocked this effect, resulting in a decrease in heart rate.

Anesthesia, Inhalation↗