Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pharmacological properties of midaglizole (DG-5128, CAS 66529-17-7) on central and peripheral nervous systems were investigated in comparison with those of tolbutamide. 1. Central nervous system: Midaglizole showed little or no effects on general behavior (mouse), spontaneous motor activity (mouse), hexobarbital anesthesia (mouse), conditioned avoidance response (rat) and body temperature (rabbit) at an oral dose of 100 mg/kg. It also produced little or no changes in electroencephalogram (cat) and spinal reflex (cat) after intravenous dosing of 10 mg/kg. The drug lacked anticonvulsant and analgesic activities (mouse). Midaglizole produced clonic convulsion, mydriasis, lacrimation, increase in pinna reflex, decrease in spontaneous motor activity, increase in pain threshold (mouse) and rise in body temperature (rabbit) at oral dose of 300 mg/kg. Tolbutamide showed similar effects except that it potentiated hexobarbital anesthesia, slightly decreased convulsion and tended to decrease body temperature. 2. Autonomic nervous system: Midaglizole potentiated the pressor response to norepinephrine and inhibited the depressor response to acetylcholine at an intravenous dose of 10 mg/kg (anesthetized dogs). Similar results were observed after dosing of tolbutamide. Midaglizole potentiated the contractile response of nictitating membrane to pre- and post-ganglionic cervical sympathetic nerve stimulation after intravenous dosing of 1 mg/kg (cat). Tolbutamide lacked the activity on the contraction elicited by both stimulations. Midaglizole and tolbutamide had little or no effect on pupil size (rabbit). 3. Skeletal muscle contraction (neuromuscular junction): Midaglizole (3-10 mg/kg i.v.) slightly potentiated the tibialis anterior muscle contraction induced by peroneal nerve stimulation, but did not potentiate the contraction by direct (muscle) stimulation (rabbit). On the other hand, tolbutamide increased the contraction induced by both nerve and muscle stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological studies with the alpha 2-adrenoceptor antagonist midaglizole. Part II: Central and peripheral nervous systems. 167 69

IRFI 016 has demonstrated significant antioxidant activity, inhibiting hepatic lipid peroxidation (rat intoxicated by CCl4) and the formation of gastric lesions by ethanol (rat). This activity proved equal to or better than that exhibited by the most investigated antioxidant/radical scavenger agents (such as BHA, BHT, Vitamin E). The drug markedly increased mucus production (rabbit, mouse) by all the administration routes used (os, i.v. and inhalatory) and proved more active than, or overlapping, the most noted mucoregulatory/mucolytic drugs (sobrerol, bromexine, thiopronine, ambroxol, N-acetylcysteine) which were chosen for comparison. The tracheo-bronchial mucus viscosity was also significantly reduced (bronchitic animals) as was the fucose and total protein content. In the pigeon, IRFI 016 improved mucociliary clearance. Moreover IRFI 016 evidenced anti-inflammatory activity nearly equal to that exhibited by ASA and phenylbutazone (carrageenin oedema, abcesses and inflammatory pain).
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PMID:2-(2,3-Dihydro-5-acetoxy-4,6,7-tribenzofuranyl)acetic acid (IRFI 016): a new antioxidant mucoactive drug. 213 8

The effects of intrathecal administration of prostaglandins on pain responses in conscious mice were evaluated by using hot plate and acetic acid writhing tests. Prostaglandin D2 (0.5-3 ng/mouse) had a hyperalgesic action on the response to a hot plate during a 3-60 min period after injection. Prostaglandin E2 showed a hyperalgesic effect at doses of 1 pg to 10 ng/mouse, but the effect lasted shorter (3-30 min) than that of prostaglandin D2. Similar results were obtained by acetic acid writhing tests. The hyperalgesic effect of prostaglandin D2 was blocked by simultaneous injection of a substance P antagonist (greater than or equal to 100 ng) but not by AH6809, a prostanoid EP1-receptor antagonist. Conversely, prostaglandin E2-induced hyperalgesia was blocked by AH6809 (greater than or equal to 500 ng) but not by the substance P antagonist. Prostaglandin F2 alpha had little effect on pain responses. These results demonstrate that both prostaglandin D2 and prostaglandin E2 exert hyperalgesia in the spinal cord, but in different ways.
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PMID:Nociceptive effects induced by intrathecal administration of prostaglandin D2, E2, or F2 alpha to conscious mice. 232 44

The effects of injecting ATP, ADP, AMP, adenosine and adenine intrathecally on the pain response induced by the injection of substance P (10 ng/mouse) intrathecally were studied. All the compounds except adenine inhibited the pain response in a dose-related manner. The ED50 values of ATP, ADP, AMP and adenosine were 2.10, 0.93, 0.88 and 0.48 micrograms/mouse, respectively. Pretreatment with theophylline at a dose of 100 mg/kg p.o. markedly diminished all the antinociceptive effects. The effect of adenosine was not affected by s.c. injection of naloxone. These results suggest the existence of adenosine receptors which modulate spinal nociceptive sensory processing, independently of the endogenous opiate system.
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PMID:Spinal antinociceptive effects of adenosine compounds in mice. 244 Jul 5

The relationship between the kaolin-induced writhing reaction and production of arachidonate metabolites (PGs) in mice was studied. PGs were released into the peritoneal cavity after intraperitoneal injection (i.p.) of kaolin (2.5 mg/mouse) with a peak at 5 min. About 80% of the total amount was 6-keto-PGF1 alpha. There was a significant correlation (r = 0.8237, p less than 0.001) between the number of writhes and the amount of 6-keto-PGF1 alpha. The writhing reaction induced by kaolin was significantly inhibited by simultaneous injection of soybean trypsin inhibitor (SBTI; 2.5 mg/mouse) and increased by simultaneous injection of captopril (50 micrograms/mouse). The writing reaction induced by kaolin which was inhibited by oral administration of indomethacin (1 mg/kg) was restored by exogenous i.p. injection of PGI2-Na (2-10 ng/mouse). Indomethacin, ibuprofen and alminoprofen inhibited the writhing reaction and reduced the level of peritoneal 6-keto-PGF1 alpha in parallel manner. Tiaramide, pentazocine and morphine inhibited the writhing reaction without reducing the revels of 6-keto-PGF1 alpha. These results differentiate the site of action of these analgesics. They suggest that the mechanism of the kaolin-induced writhing reaction in mice involves a synergic pain caused by simultaneously released bradykinin and PGI2. This model is a useful tool which allows differentiation of mode of action of analgesics by simultaneous determination of the writhing response and peritoneal 6-keto-PGF1 alpha.
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PMID:Involvement of prostaglandins in kaolin-induced writhing reaction in mice. 251 71

The writhing reaction in mice induced by kaolin, a factor XII activator, was studied. An intraperitoneal injection of kaolin clearly induced a writhing reaction in a dose-dependent fashion, and the reaction disappeared about 10-15 min later. The writhing reaction reached a peak at 5-10 min after the injection of kaolin (0.5 ml/mouse, i.p.; 5 mg/ml saline). A simultaneous intraperitoneal injection of soybean trypsin inhibitor (SBTI, 2.5 mg/mouse) almost completely suppressed the writhing reaction caused by kaolin (2.5 mg/mouse) for the first 10 min. The kaolin-induced writhing reaction was markedly potentiated by a simultaneous intraperitoneal injection of captopril (50 micrograms/mouse). At 60 min after kaolin injection during the disappearance of the writhing reaction, the reaction reappeared when captopril was injected, but reactions observed at this later stage were completely blocked by SBTI. Indomethacin, ibuprofen and alminoprofen inhibited the writhing reaction dose-dependently. Kaolin thus induces a clear and reproducible writing reaction, which might be mainly dependent on the action of bradykinin via activation of factor XII, and should prove to be a simple and convenient model of bradykinin-induced pain for the assessment of analgesic actions.
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PMID:A new writhing model of factor XII activator-induced pain for assessment of non-steroidal anti-inflammatory agents. I. Kaolin-induced writhing in mice. 266 95

Hyperalgesic actions in mice of intracerebroventricularly (i.c.v.) administered arachidonic acid, prostaglandin (PG) E2, PG F2 alpha and PG D2 were studied. For the analgesic assay, the mouse tail pressure method was employed. The i.c.v. administration of arachidonic acid (0.01-100 micrograms/mouse), PG E2 (0.01-100 ng/mouse), PG F2 alpha (0.1-1000 ng/mouse) and PG D2 (0.1-1000 ng/mouse) decreased the pain threshold in a dose dependent manner. The doses that produced the maximal decrease in pain threshold for arachidonic acid, PG E2, PG F2 alpha and PG D2 were 10 micrograms/mouse, 10 ng/mouse, 100 ng/mouse and 100 ng/mouse, respectively. Acidic nonsteroidal antiinflammatory drugs (NSAIDs) produced much more potent analgesic effects in arachidonic acid-induced hyperalgesic mice than in normal mice and in PG E2-, PG F2 alpha- and PG D2-induced hyperalgesic mice, but nonacidic NSAIDs and morphine produced the same analgesic effect in both hyperalgesic and normal mice. Linoleic acid, linolenic acid and gamma-linolenic acid induced weak hyperalgesia, but this unsaturated fatty acids-induced hyperalgesia was not affected by indomethacin (2 mg/kg, p.o.). These findings indicate that the arachidonic acid and its metabolites were related to mediation or modulation of central pain pathways and that the central nervous system may be partially involved in the action of acidic NSAIDs.
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PMID:Hyperalgesic action in mice of intracerebroventricularly administered arachidonic acid, PG E2, PG F2 alpha and PG D2: effects of analgesic drugs on hyperalgesia. 310 73

Intraperitoneal injection of zymosan (1 mg in 0.5 ml saline) in mice induces a transient writhing response accompanied by the synthesis of small amounts of prostaglandin E2(PGE2, less than 2 ng) and larger amounts of PGI2 (200 ng per mouse), measured as its non-enzymatic breakdown product, 6-keto-PGF1 alpha. Although both centrally-acting analgesics (morphine, clonidine) and prostaglandin biosynthesis inhibitors (aspirin, indomethacin, ibuprofen) blocked the writhing response to intraperitoneal injection of zymosan, only the latter reduced prostaglandin levels in the peritoneal cavity. The writhing response correlated equally well with PGE2 levels and 6-keto-PGF1 alpha levels when data from mice treated with centrally-acting analgesics were excluded. However, intraperitoneal injection of PGI2, but not PGE2, reversed the analgesia induced by indomethacin in zymosan-injected mice. Centrally-acting agents, but not ibuprofen, blocked the ability of PGI2 to reverse the analgesic activity of indomethacin. PGI2 (2 micrograms per mouse), injected intraperitoneally in otherwise untreated mice, induced writhing. These data indicate that PGI2 is the prostaglandin involved in mediation of the writhing response to zymosan and that prostaglandin biosynthesis inhibitors, but not centrally-acting analgesics, exert their analgesic activity by reducing the peritoneal level of PGI2. It is possible that PGI2 may have the ability to stimulate pain receptors directly in the mouse peritoneal cavity, in addition to its previously recognized ability to sensitize pain receptors to other pain-producing stimuli.
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PMID:The role of prostaglandins in the nociceptive response induced by intraperitoneal injection of zymosan in mice. 359 81

In the tail-flick test in mice, the intraventricular administration of Substance P (10-5,000 ng/mouse) produced a naloxone-reversible analgesic effect of rapid onset and long duration. The dose-response curve was bell-shaped, the analgesic effect being smaller after the largest doses. The analgesia was blocked by concomitant intraventricular administration of the antibody against met-enkephalin but not by the antibody against beta-endorphin. In the hot plate assay, Substance P produced analgesia in mice with high sensitivity to pain, and hyperalgesia in mice with lower sensitivity to pain than normal. The analgesia was blocked by the antibody against met-enkephalin but the hyperalgesia or the scratching response were not modified by the antiserum. The results appear to indicate a dual effect, analgesic or hyperalgesic, of Substance P in mice, the former probably being mediated by release of met-enkephalin.
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PMID:Blockade by met-enkephalin antiserum of analgesia induced by substance P in mice. 618 74

The general pharmacological study of iodixanol, a non-ionic isotonic contrast medium, was conducted. 1) Iodixanol administered intravenously over a dose range of 320 to 3,200 mgI/kg had little or no effect on the general behavior, spontaneous locomotor activity, hexobarbital sleeping time, pain response, electroshock- or pentylenetetrazol-induced convulsion (mouse), EEG or body temperature (rabbit), gastrointestinal propulsion (mouse) or skeletal muscle contraction (rabbit). Iodixanol had no specific interaction with acetylcholine, histamine, serotonin, nicotin, BaCl2 (ileum), methacholine (trachea), isoprenaline (atrium) or oxytocin (pregnant uterus), nor had any effect on spontaneous contractility (atrium and uterus), or transmural electrostimulation-induced contractility (vas deferens) at concentrations of < or = 3.2 x 10(-3) gI/ml in vitro. Iodixanol had no effect on the cardiovascular system of dog, except that it increased femoral blood flow and respiratory rate at doses of > or = 1,000 mgI/kg. Iodixanol at 3,200 mgI/kg i.v. reduced urine output with a decrease in Na+ and Cl- excretion, whereas at 320 mgI/kg i.v., it slightly increased urine output (rat). 2) Injections of iodixanol into the cerebroventricular (0.96, 9.6 mgI/mouse and 3.2, 32 mgI/rat), left ventricular (1,920, 6,400 mgI/dog) or coronary artery (640, 1,920 mgI/dog) had no conspicuous effect on the central nervous system or the cardiovascular system, respectively. There was no marked difference among iodixanol, iohexol and iopamidol in this respect. Vascular pain during injection into the femoral artery (300-320 mgI/guinea pig) appeared to be less intense with iodixanol, compared with the other contrast media iohexol and iopamidol. These results suggest that intravenous injection of iodixanol is relatively free from pharmacological activity, and effects of iodixanol on the central nervous system (intracerebroventricular injection) and cardiovascular system (intra-left ventricular and -coronary injections) are comparable to those of iohexol and iopamidol. Furthermore, intra-femoral injection of iodixanol has less of a tendency to produce vascular pain than those of iohexol and iopamidol.
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PMID:[General pharmacological study of iodixanol, a new non-ionic isotonic contrast medium]. 749 Jul 85


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