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Biomedical subjects

R J Sheldon

Publications and source records attributed to R J Sheldon.

26 records · Page 2Linked to original sources
PubMed1987

A comparison of the central gastrointestinal antitransit effects of morphine and bombesin in the mouse.

The gastrointestinal motor effects of centrally-given morphine and bombesin were compared in mice. Both compounds produced a dose-related decrease in the propulsion of a marker along the gut when given by the intracerebroventricular (i.c.v.) or intrathecal (i.th.) routes. Co-administration of the same compound by both routes was found to produce a marked increase in potency for morphine, but only a slight increase in potency for bombesin. Isobolographic analysis of the gut effects of these compounds revealed a multiplicative brain-spinal cord interaction for morphine, but an additive interaction for bombesin. These results are consistent with the interpretation that morphine can act at either the level of the brain or the spinal cord, activating independent pathways which ultimately converge to alter gut propulsion. In contrast, spinal bombesin requires communication to supraspinal sites in order for its gut effects to occur, suggesting activation of a common outflow pathway from the central nervous system.

Animals↗
PubMed1987

Mu antagonist properties of kappa agonists in a model of rat urinary bladder motility in vivo.

The possibility that the kappa agonists, U50,488H, ethylketazocine and tifluadom, might act as opioid antagonists was studied using the inhibition of the anesthetized rat micturition reflex in vivo as a pharmacological endpoint. Intracerebroventricular administration of equieffective doses of the mu agonists [D-Ala2, NMePhe4, Gly-ol]enkephalin (0.01 nmol), [N-MePhe3, D-Pro4]enkephalin (0.03 nmol), morphine (0.08 nmol), normorphine (0.3 nmol), sufentanil (0.002 nmol), etorphine (0.004 nmol), phenazocine (17 nmol) and meperidine (176 nmol) inhibited spontaneous bladder contractions for a duration of approximately 20 to 30 min. Similarly, i.c.v. administration of the delta-selective agonist (D-Pen2, D-Pen5]enkephalin (15 nmol) inhibited the micturition reflex for approximately the same duration. The kappa agonists U50,488H (22 nmol), ethylketazocine (3 nmol) and tifluadom (3 nmol) did not alter bladder activity after i.c.v. administration. Higher doses of ethylketazocine (10 nmol) or tifluadom (20 nmol), but not U50,488H, produced consistent suppression of bladder contractions. Pretreatment of rats (-15 min, i.c.v.) with doses of U50,488H, ethylketazocine or tifluadom which did not produce an agonist effect consistently blocked the inhibitory actions of the mu agonists morphine and normorphine on bladder motility, but failed to antagonize the similar actions of the mu agonists [D-Ala2, NMePhe4, Gly-ol]enkephalin, [N-MePhe3, D-Pro4]enkephalin, phenazocine, meperidine or those of the delta agonist [D-Pen2, D-Pen5]enkephalin. Centrally initiated bladder effects of the mu agonists etorphine and sufentanil were antagonized by U50,488H but unaffected by ethylketazocine or tifluadom. In addition, administration of U50,488H (i.c.v.) during a morphine-induced bladder shutdown resulted in either an immediate recovery of bladder activity or a shortened duration of action.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1983

The effects of hyperosmolar solutions on isolated vascular smooth muscle examined with verapamil.

Hyperosmotic sucrose solutions elicited tension from rat aortic strips in direct proportion to osmolarity. Norepinephrine-induced tension was reduced in proportion to increases in osmolarity; however, reduction of barium-induced tension by hyperosmolar solutions was minimal. Norepinephrine-induced tension is primarily dependent on intracellular calcium mobilization, while barium-induced tension is primarily dependent on extracellular calcium influx. Therefore, hyperosmolar solutions may alter vasoconstriction associated with intracellular calcium mobilization rather than that associated with extracellular calcium influx. In the presence of verapamil which blocks calcium entry into muscle, barium-induced tension was eliminated while the direct tension elicited by hyperosmolar solutions was slightly affected (6% reduction) and the inhibitory effect of hyperosmolar solutions on norepinephrine-induced tension was still observed. In contrast, the tension elicited by hyperosmolar solutions was greatly reduced by papaverine which promotes sequestration of myoplasmic calcium to cause relaxation. The vascular effects of hyperosmolar solutions may be due to alterations in the intracellular calcium rather than the extracellular calcium utilized by vasoconstricting agents.

Animals↗
PubMedDate not supplied

In vivo and in vitro studies with agents that cause quasi-morphine withdrawal syndromes.

Compounds that elicit a "quasi-morphine withdrawal syndrome" (QMWS) after acute administration to rats constitute a new class of behavior-modifying agent. In studying the pharmacological bases of quasi-opiate withdrawal syndromes, we found that the dihydrocodeinone, RX 336-M, a standard QMWS-inducing agent, caused a naloxone-insensitive increase in twitch tension on the field-stimulated rat was deferens preparation. In contrast, IBMX (3-isobutyl-1-methylxanthine), the historical inducer of quasi-abstinence in rats, gave a naloxone-insensitive decrease in twitch tension. Tolerance developed to the "wet-dog" shakes elicited by twice-daily s.c. injections of RX 336-M or IBMX in rats for 5 or 15 days, respectively. The parallel development of tolerance to the in vitro effects of these compounds could not be demonstrated.

1-Methyl-3-isobutylxanthine↗