Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

AHR-10037 is an anti-inflammatory compound possessing analgesic and antipyretic properties and a high therapeutic index. AHR-10037 was comparable to indomethacin in suppressing acute (Evans blue-carrageenan pleural effusion) and chronic (adjuvant-induced arthritis) inflammation. There was a delayed onset of antipyresis (yeast-induced hyperthermia in rats), analgesia (acetylcholine-induced abdominal constriction in mice) and inhibition of caster oil-induced diarrhea in rats. Antipyresis occurred 3 hours after administration of AHR-10037, 4 mg/kg, PO. vs 1 hour after administration of acetylsalicylic acid, 100 mg/kg, PO; maximum analgesic activity (ED50 = 4.1 mg/kg) occurred at 4 hours. AHR-10037 was inferior to indomethacin in suppressing castor oil-induced diarrhea in rats. The therapeutic index of AHR-10037 (relating acute anti-inflammatory potency to gastric toxicity potency relative to indomethacin) ranged from 56-91. The pharmacological profile suggests that AHR-10037 is a prodrug converted in vivo to a cyclooxygenase inhibitor.
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PMID:AHR-10037, a non-steroidal anti-inflammatory compound of low gastric toxicity. 228 17

The effect of intrathecal pertussis toxin on morphine dependence was studied in rats suffering from chronic pain (Freund's adjuvant-induced arthritis). Animals were rendered tolerant-dependent by subcutaneous implantation of 3 pellets of 75 mg morphine base each. In both, normal and arthritic animals, 1 microgram pertussis toxin reduced the analgesia induced by morphine in the tail-flick test. Naloxone (1 mg/kg, s.c.) precipitated a withdrawal syndrome in arthritic animals that was milder in respect to the one produced in normal rats. Pretreatment with pertussis toxin significantly diminished the incidence of withdrawal signs such as jumps, squeak on touch, chattering, ptosis, body shakes and diarrhoea in tolerant-dependent normal rats, while this effect could not be observed in animals suffering from chronic pain. This differential activity of the toxin could be due to the altered tonus of certain neurotransmitter systems that accompanies the chronic situation of pain.
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PMID:Intrathecal pertussis toxin attenuates the morphine withdrawal syndrome in normal but not in arthritic rats. 230 75

We evaluated the ability of mu [morphine, Tyr-Pro-N-MePhe-D-Pro-NH2 (PLO17)], delta (Tyr-D-Pen-Gly-Phe-D-Pen) (DPDPE) and kappa [U50,488H, (trans-3,4-dichloro-N-methyl-N-(2-(1-pyr-rolidinyl) cyclo-hexyl)benzeneacetamine)] opioid receptor selective agonists to inhibit diarrhea induced by castor oil (0.6 ml p.o.) in mice after supraspinal (i.c.v.) and peripheral (s.c.) administration. The antidiarrheal potency of each compound was compared to its analgesic and gastrointestinal antitransit potency when given by the same route of administration. When administered i.c.v., morphine, PLO17 and DPDPE inhibited diarrhea in a dose-related fashion. The mu agonists, morphine and PLO17, given i.c.v, inhibited diarrhea at doses much lower than those needed to produce analgesia or to inhibit gastrointestinal transit. DPDPE (i.c.v.) was equipotent in inhibiting diarrhea and in eliciting analgesia, but did not effect the rate of transit. U50,488H (i.c.v.) inhibited diarrhea only at extremely high doses which also caused profound postural-motor incapacitance. U50,488H given i.c.v. had no effect on transit at any dose. When given peripherally, morphine, PLO17, DPDPE and U50,488H all inhibited diarrhea in a dose-related fashion. All four compounds inhibited diarrhea at doses much below those needed to cause analgesia. Morphine s.c. and PLO17 s.c. both inhibited diarrhea at doses lower than those required to inhibit transit. DPDPE s.c. and U50,488H s.c. had no effect on transit at any dose. The antidiarrheal effects of i.c.v. morphine, i.c.v. PLO17 and i.c.v. DPDPE were antagonized by pretreatment with 1 microgram i.c.v. of naltrexone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antidiarrheal properties of supraspinal mu and delta and peripheral mu, delta and kappa opioid receptors: inhibition of diarrhea without constipation. 254 Mar 24

A combination of the antigestagen mifepristone (RU 486) and a synthetic prostaglandin analogue, gemeprost, was used to induce therapeutic abortion in 100 women in early pregnancy. Local family planning services and general practitioners in Edinburgh referred women of less than 56 days' amenorrhea who had requested abortion. Pregnancy was confirmed by measurement of the serum level of human chorionic gonadotropin. Group I (n=20) received 150 mg mifepristone orally each day for 4 days. Groups II (n=30), III (n=30), and IV (n=20) received a single oral dose of mifepristone, 400 mg, 500 mg, or 600 mg, respectively. Samples of peripheral blood were collected at recruitment for measurement of the concentration of hemoglobin, urea, electrolytes, cortisol, and HCG and for liver function tests. Blood also was taken for estradiol and progesterone essay from women in Groups II, III, and IV. Each woman recorded symptoms in a diary from the day prior to the start of treatment. Study participants were reviewed 1, 2, and 4 weeks after treatment and discharged from followup after the onset of the next menstrual period. The effectiveness of the 4 treatment regimens was similar. Only 10 (14%) of the 74 women who received half a gemeprost pessary required the 2nd half. 95 of the women aborted completely; 5 women needed surgical intervention. Data were pooled for analysis because there was no significant difference between the 4 groups in the onset of bleeding and pain, requirement for analgesia, side effects, duration of bleeding, measured blood loss, and the time until the next menstrual period. The 94 women who experienced pain became aware of pelvic discomfort 46.6 hours after the initiation of treatment. No patient needed analgesia during the first 48 hours of treatment. After insertion of the pessary, 44 women received an oral analgesic drug and 9 an intramuscular opioid. 47 women did not need an analgesia. There was no significant difference in the frequency of nausea before and during treatment, but there was a significant increase in the incidence of vomiting and of diarrhea. 30 women vomited after the pessary was inserted compared with 13 the day before treatment; 10 women had diarrhea compared with 3 before treatment. No women had clinical evidence of pelvic infection. Liver function tests and cortisol levels were similar prior to and following treatment. Levels of HCG, and estradiol and progesterone decreased significantly after treatment. There were no significant differences in the results between those who needed evacuation and those who did not.
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PMID:Induction of therapeutic abortion in early pregnancy with mifepristone in combination with prostaglandin pessary. 289 91

During pregnancy the uterus is maintained in a quiescent state by the secretion of progesterone. Antigestagens antagonize the biological action of progesterone by binding to the nuclear receptor in the target organs. Administration of the antigestagen mifepristone to women induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. In addition, the sensitivity of the myometrium to exogenous prostaglandins is markedly increased. Although mifepristone will induce bleeding in the majority of women in early pregnancy, the incidence of incomplete abortion or ongoing pregnancies increases with increasing gestational age and is too high to be clinically useful as an agent for therapeutic abortion. However, a single dose of mifepristone (400-600 mg) followed by a vaginal pessary of a prostaglandin analogue (0.5-1.0 mg), gemeprost, induced complete abortion in 95 of 100 women of gestational age less than 42 days (less than or equal to 56 days amenorrhoea). The incidence of diarrhoea (15%) and abdominal pain requiring opiate analgesia (10%) was much lower than when abortion was induced with prostaglandin alone. Vaginal bleeding continued for 13.8 +/- 0.8 days after administration of the prostaglandin. A combination of an antigestagen with a small dose of a prostaglandin analogue is an effective alternative to vacuum aspiration for the therapeutic termination of early pregnancy.
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PMID:Prostaglandins and antigestagens for the interruption of early pregnancy. 319 7

The peripheral activity of the quaternary narcotic antagonist N-methyl levallorphan-methane sulphonate (SR 58002 C) at opioid sites located in the periphery and in the central nervous system (CNS), was studied by different approaches in rats after subcutaneous injection (s.c.). Pretreatment with SR 58002 C 2,8 or 32 mg/kg s.c. 10, 50 or 110 min before buprenorphine consistently reduced buprenorphine in vivo binding only in the small intestinal longitudinal muscle with attached myenteric plexus (MP), whereas naloxone (1 mg/kg s.c.) 10 min before buprenorphine lowered buprenorphine binding in MP and brain (without cerebellum). Plasma levels were not altered by SR 58002 C or naloxone. The same doses of SR 58002 C injected 10, 50 or 110 min before morphine selectively antagonized the inhibition of transit of a charcoal meal along the small intestine (mainly a peripheral effect) induced by the agonist, but did not antagonize morphine-elicited analgesia in the hot-plate test (central effect). Naloxone (1 mg/kg s.c.) injected 10 min before morphine antagonized both agonist effects simultaneously. In morphine-dependent rats SR 58002 C (0.25, 1, 4 and 32 mg/kg s.c.) induced diarrhea, dose-dependently, in most animals within the first 30 min, while jumping, measured in the same rats, occurred in some animals, not dose-dependently, from 60 min on. Naloxone (1 mg/kg s.c.) induced both effects in most rats. These findings suggest that, although SR 58002 C probably penetrates the blood-brain barrier in some morphine-dependent rats, it discriminates peripheral and CNS opioid effects.
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PMID:Antagonism by N-methyl levallorphan-methane sulphonate (SR 58002 C) of morphine-elicited acute and chronic central and peripheral effects. 338 93

The termination of early pregnancy (less than 56 days amenorrhoea) has been investigated using 16,16-dimethyl-trans-delta 2-PGE, methyl ester in a controlled release preparation. The onset of crampy abdominal pain was seen after 270 +/- 39 minutes and bleeding occurred after 603 +/- 95 minutes. Two (15%) patients required no pain relief during treatment, however 5 (38%) requested oral analgesia, and in 6 (46%) individuals the pain was severe enough to warrant parenteral opiates. The overall success rate for complete abortion was 85%. No serious adverse effects were seen, but vomiting occurred in 2 (15%) women, and diarrhoea in 3 (23%). Although the use of this prostaglandin analogue in slow release form provides an effective treatment method for early abortion using a reduced total dose of prostaglandin, the acceptability of the drug as an agent for menstrual induction continues to be limited by the occurrence of troublesome gastro-intestinal side effects.
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PMID:A controlled release form of 16,16-dimethyl-trans-delta 2-PGE, methyl ester for early abortion. 369 93

This study determines the efficacy and incidence of side effects associated with intravaginal prostaglandin F2alpha (PGF2alpha). 20 healthy patients (16 to 30 years of age; 9-16 weeks gestational age) with no history of threatened abortion in the current pregnancy were studied. Baseline hematologic, metabolic, urinary, and hormonal studies were conducted. Transabdominal amniocentesis was performed in 7 patients. The uterus was observed for spontaneous contractility. Lactose tablets with 50 mg PGF2alpha (THAM salt) were administered vaginally. The intensity and frequency of uterine contractions in the 7 monitored patients determined the treatment regimen. Prostaglandin tablets were inserted at hourly intervals to maintain frequency of contractions at 5 per 10 minute time interval and/or intensity of contractions greater than an average of 40 mm Hg over a 10 minute-period. 13 patients whose uterine activity during the abortion process was assessed by clinical observation were given a similar time schedule. Blood studies were peformed 6 hours after the onset of therapy and immediately following abortion. Analgesia were used intramuscularly as antiemetic agents where necessary. Prepared questionnaires and personal interviews were completed at the 4-week clinic visit to determine patient acceptability of the method. 19 of 20 patients aborted, with 7 classified as complete and the remaining 12 requiring a uterine exploration and curettage for removal of retained placental fragments. Average induction-complete abortion interval was 17 hours and 50 minutes. There was no difference between multiparous and primiparous patients. In 1 patient who failed to abort with the prostaglandin tablet, administration of 900 mg PGF2alpha and hypertonic saline were used to facilitate abortion which occurred 24 hours later. Emesis occurred in 18 patients, diarrhea in 13, and fever in 11. Of 15 patients who agreed to an interview during the clinic visit, 14 stated they would choose the method again. Vaginal administration of PGs appears to exert effects by systemic, rather than by local mechanism. Although this method is effective, it has a high incidence of side effects and is associated with increased utilization of professional time.
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PMID:Abortifacient efficacy of intravaginal prostaglandin F2 . 468 31

This study combined the use of preinjection laminaria, intravenous oxytocin, and 15 mg of intra-amniotic prostaglandin (PG) F2alpha in order to demonstrate a potentially improved procedure for 2nd trimester abortion. 20 patients, aged 18-27, were between the 16-20 weeks gestation, and were free of intercurrent medical or obstetrical problems. 7 of the 20 were nulliparae. A laminaria was inserted into the cervix the evening before the injection of PG. In the morning an intravenous infusion was begun using 50 units of oxytocin in 500 ml of 5% dextrose and 0.9% sodium choloride at a rate of 150 ml/hour. The amniocentesis was performed and when a free flow of clear amniotic fluid was obtained 15 mg. of PGF2alpha was injected into the amniotic cavity. Different concentrations of oxytocin were administered if contractions were increasingly painful or not. Results of the experiment were that: 1) all patients aborted within 24 hours of the prostaglandin injection, 2) the median injection-to-abortion interval was 7 hours and 25 minutes; primigravidae aborted with a median time of 15 hours 20 minutes; and multiparous patients aborted in 6 hours 20 minutes; 3) only 9 patients requested analgesia medication; 4) the average blood loss was 150-200 nl; 1 patient had a postabortion hemorrhage greater than 500 ml; 5) 3 patients underwent sharp curettage for suspected retained secundines; 6) vomiting occurred in 6 patients, 3 of whom had emesis once; and 7) no diarrhea was encountered during the study. This study demonstrates that this procedure fulfills 3 strict criteria for success, as follows: 1) single injection technic, 2) consistent abortion within 24 hours, and 3) minimal side effects.
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PMID:Midtrimester abortion using prostaglandin F2alpha, oxytocin, and laminaria. 471 13

Vaginal suppositories containing (15S)-15-methyl prostaglandin F2 alpha methyl ester were administered to 40 subjects, in an attempt to induce an early abortion. All subjects were 49 days or less from their last menstrual period. Ten subjects received a 3-mg suppository followed in 3 hours by a 1 mg suppository, ten subjects received the 1-mg suppository followed in 3 hours by a 3-mg suppository, and twenty subjects received the 3-mg suppository followed in 1 hour by the 1-mg suppository. Twenty-four subjects (60%) had a successful termination of their pregnancy using the two vaginal prostaglandin suppository regimen. All subjects who aborted had 10 percent or less of their pretreatment levels of beta-hCG 7 to 22 days after therapy. Sixteen subjects (40%) did not abort. One of the subjects who failed treatment refused the second suppository due to gastrointestinal side effects and uterine cramping following the insertion of the 1-mg suppository. A second subject had an incomplete abortion and developed mild endometritis. Sixteen subjects reported side effects which included nausea, emesis, diarrhea, uterine cramping requiring analgesia, restlessness, shakiness, and dizziness. The addition of the second vaginal suppository containing this particular prostaglandin analogue did not significantly increase the overall abortifacient activity of this method.
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PMID:Termination of early gestation with (15S)-15-methyl prostaglandin F2 alpha methyl ester vaginal suppositories. 617 57


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