u-50488 has been researched along with methylnaltrexone* in 3 studies
3 other study(ies) available for u-50488 and methylnaltrexone
Article | Year |
---|---|
Gastric effects of methylnaltrexone on mu, kappa, and delta opioid agonists induced brainstem unitary responses.
In this study, we evaluated the gastric effects of methylnaltrexone, an opioid receptor antagonist that does not cross the blood-brain barrier in vivo, on mu, kappa and delta opioid agonists induced brainstem unitary responses in an in vitro neonatal rat brainstem-gastric preparation. Single units in the medial subnucleus of the nucleus tractus solitarius (NTS), responding to electrical stimulation of subdiaphragmatic vagal fibers, were recorded. Selective opioid receptor agonists and antagonists were applied only to the gastric compartment of the bath chamber and thus, the brainstem functions of the preparation were not affected by the drugs. The peripheral gastric effects of a mu opioid receptor agonist, DAMGO, and a kappa opioid receptor agonist, U-50,488H, were evaluated on 58 tonic units that received the subdiaphragmatic vagal inputs. For approximately 78% of the units observed, DAMGO (1.0 microM) and U-50,488H (1.0 microM) induced a concentration-dependent inhibition of 62.1+/-9.3% (mean +/- SE) and 49.2+/-6.5% of the control level of the NTS neuronal activity, respectively. Methylnaltrexone competitively antagonized the DAMGO-induced brainstem neuronal effects. Methylnaltrexone at an 18.8-fold higher concentration also reversed U-50,488H-induced NTS neuronal responses. Naloxone, a non-selective opioid receptor antagonist, reversed the inhibitory effects of DAMGO and U-50,488H at much lower concentrations (3.8% and 0.5%, respectively) compared to methylnaltrexone. Only 18% of the NTS neurons evaluated showed inhibitory responses to a delta receptor agonist, DPDPE, (19.7+/-5.0% at 10 microM), and this inhibition could not be reversed by methylnaltrexone in the concentration range we tested. In addition, when methylnaltrexone (1.0 microM) alone was applied to the gastric compartment, there was an activation (8.5+/-2.1%) of the NTS neurons receiving subdiaphragmatic vagal inputs, suggesting an endogenous gastric opioid action in the modulation of brainstem neuronal activities. Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Animals, Newborn; Brain Stem; Electric Stimulation; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, D-Penicillamine (2,5)-; Enkephalins; Morphine; Naltrexone; Narcotic Antagonists; Neurons; Quaternary Ammonium Compounds; Rats; Rats, Sprague-Dawley; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu; Solitary Nucleus; Stomach; Vagus Nerve | 1999 |
Systemic administration of dynorphin A-(1-13) markedly improves cycloheximide-induced amnesia in mice.
The effects of systemic or intracerebroventricular injection of dynorphin A-(1-13), a kappa-selective opioid receptor agonist, on cycloheximide-induced amnesia were investigated by using a step-down-type passive avoidance task in mice. The intracerebroventricular injection of dynorphin A-(1-13) (0.3-3 micrograms) before training significantly prolonged step-down latency. The systemic administration of dynorphin A-(1-13) (1, 3 and/or 10 mg/kg, i.p.) before training or retention tests markedly inhibited the cycloheximide (30 mg/kg, s.c.)-induced shortening of step-down latency, indicating antiamnesic effects of dynorphin A-(1-13). One and 3 mg/kg doses of ((+/-)trans-3, 4-dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, methanesulfonate hydrate (U-50,488H), another kappa-selective opioid receptor agonist, significantly inhibited the shortening. The anti-amnesic effects of dynorphin A-(1-13) (3 and 10 mg/kg, i.p.) were almost completely antagonized by intracerebroventricular administration of the quaternary derivative of the opioid receptor antagonist naltrexone methobromide (0.3 microgram), but not by systemic administration of the opioid receptor antagonist (1 mg/kg, s.c.), demonstrating central mediation of the anti-amnesic effects of dynorphin A-(1-13). Furthermore, the kappa-selective opioid receptor antagonist, nor-binaltorphimine (2 mg/kg, s.c.), almost completely antagonized the effects of dynorphin A-(1-13) (3 and 10 mg/kg, i.p.). These results suggest that dynorphin A-(1-13) produces anti-amnesic effects through the blood-brain barrier. Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Amnesia; Analgesics; Animals; Avoidance Learning; Cycloheximide; Dynorphins; Injections, Intraventricular; Male; Memory; Mice; Naltrexone; Narcotic Antagonists; Protein Synthesis Inhibitors; Pyrrolidines; Quaternary Ammonium Compounds; Receptors, Opioid, kappa | 1996 |
Roles of central and peripheral mu, delta and kappa opioid receptors in the mediation of gastric acid secretory effects in the rat.
The opioid receptors involved in the mediation of gastric acid secretory effects were studied in the pylorus-ligated rat. The effects of i.c.v. and i.v. administration of morphine and mu ([D-Ala2, NMePhe4, Gly5-ol]enkephalin and Tyr-Pro-NMePheD-Pro-NH2)-, delta ([D-Pen2,D-Pen5]enkephalin)- and kappa-selective [trans-3,4-dichloro-N-methyl-N-[2-91-pyrrolidinyl)-cyclohexyl]- benzeneacetamide methanesulfonate (U-50,488H), dynorphin-(1-9), dynorphin-(1-17), nalorphine, alpha-neoendorphin and ethyl-ketocyclazocine) opioid receptor agonists on gastric volume and acid output were examined. Morphine, [D-Ala2, NMePhe4, Gly5-ol]enkephalin and Tyr-Pro-NMePhe-D-Pro-NH2 decreased gastric acid secretion more potently after i.c.v. than after i.v. administration. The inhibitory effect of i.v. administered morphine on gastric acid secretion was not blocked by the quaternary opioid antagonist naltrexone methylbromide when given s.c. However, when naltrexone methylbromide was administered i.c.v., it blocked completely the effects of i.c.v. morphine and partially antagonized the effects of i.v. morphine, indicating a central site of action for morphine. The delta-selective agonist [D-Pen2,D-Pen5]enkephalin did not alter gastric acid secretion after i.c.v. or i.v. administration. The kappa-selective opioid agonist U-50,488H produced a dose-dependent increase in gastric acid secretion after i.v. but not i.c.v. administration. The other kappa-selective agonists tested did not produce a significant increase in gastric acid secretion after i.c.v. or i.v. administration. The increase in gastric acid secretion produced by U-40,488H was blocked by pretreatment with the opioid receptor antagonist naloxone, the nonselective muscarinic receptor antagonist atropine and the M1 selective muscarinic receptor antagonist pirenzepine.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Brain; Cyclazocine; Endorphins; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, D-Penicillamine (2,5)-; Enkephalins; Ethylketocyclazocine; Gastric Acid; Male; Morphine; Naltrexone; Pyrrolidines; Quaternary Ammonium Compounds; Rats; Rats, Inbred Strains; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu | 1988 |