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Investigation on the relationship between cannabinoid CB1 and opioid receptors in gastrointestinal motility in mice.

1. This study investigated whether (a) cannabinoid CB(1) receptor knockout (CB(1)(-/-)) mice displayed altered gastrointestinal transit and (b) cannabinoid CB(1) and opioid receptors functionally interact in the regulation of gastrointestinal transit. 2. Gastrointestinal transit was assessed by the Whole Gastrointestinal Transit, measuring the excretion time of an intragastrically administered marker (whole intestine), and the Upper Gastrointestinal Transit, measuring the distance covered by the marker in the small intestine. 3. CB(1)(-/-) and homozygous CB(1)(+/+) (CB(1)(+/+)) mice did not differ in both whole gut and small intestine transit. CB(1)(-/-) and CB(1)(+/+) mice were equally responsive to the inhibitory effect of morphine (10 mg kg(-1)) and loperamide (3 mg kg(-1)) on whole gut transit.4. Additionally, in CD1 mice the cannabinoid CB(1) receptor antagonist, rimonabant (0-0.5 mg kg(-1)), failed to block the inhibitory effect of morphine (0-1.25 mg kg(-1)) and loperamide (0-0.5 mg kg(-1)) on transit in small and whole intestine. Similarly, the opioid receptor antagonists, naloxone (0-1 mg kg(-1)) and naltrexone (0-10 mg kg(-1)), failed to block the inhibitory effect of the cannabinoid WIN 55,212-2 (0-3 mg kg(-1)) on transit in small and whole intestine.5. These results suggest that (a) compensatory mechanisms likely developed in CB(1)(-/-) mice to overcome the lack of inhibitory function of endocannabinoid system; (b) cannabinoid and opioid receptor systems did not interact in regulating gastrointestinal transit in mice.

Animals↗

Effect of traumatic spinal cord transection on human upper gastrointestinal motility and gastric emptying.

Whether transection of the spinal cord, above the level of the sympathetic outflow to the gastrointestinal tract, alters human upper gastrointestinal function is yet unknown. In 5 patients with complete high-cord transection (neurologic level above T1), 3 patients with complete low-cord transections (neurologic level T10 or below), and 4 age- and sex-matched healthy controls, the duration of the phases and cycle length of the interdigestive motor complex were similar. However, the percentage of phase III's of the interdigestive motor complex that originated in the antrum and propagated to the duodenum was significantly decreased in patients with high-cord transections compared with healthy subjects (38% vs. 90%; p less than 0.05), but was similar in patients with low-cord transections and normal controls (75% vs. 90%). After liquid meals, 3 of the 3 high-cord patients tested had reduced cumulative gastric emptying at 60 min postprandially compared with healthy subjects. Thus, interruption of the cervical cord above the level of the sympathetic outflow to the gastrointestinal tract disturbs normal interdigestive antral-duodenal motor coordination and may delay postprandial gastric emptying of liquid meals.

Adult↗

Modifiers of gastrointestinal motility of cattle.

Little clinically relevant, evidence-based data about the effect of motility modifiers on the GI tract of cattle are currently available. Additionally, some of the published results seem to be contradictory. Three main facts explain this apparent discrepancy: (1) Results may not be transferred from one species to another, because presence, concentration, location, distribution, and function of specific receptors may differ significantly among species. (2) The lack of a significant effect on smooth muscle preparations in vitro does not necessarily exclude a certain drug's motility-modifying property on affected animals in vivo. Certain drugs bind to receptors outside the myenteric plexus. Others, such as lidocaine and adrenergic-, dopaminergic-, and opioid-antagonists increase only GI motility, if inhibitory reflexes or a hyperactive state of the inhibitory sympathetic nervous system preexists. (3) Effects of motility modifiers as found in healthy experimental animals in vivo may not be similar to those found in spontaneously diseased animals. Accurate and reliable data on the effect of modifiers of GI motility of cattle will be obtained only from double-blinded, evidence-based, in vivo studies on spontaneously affected animals. Because well-documented results from such studies are extremely rare, intensive research in this field is warranted in the future.

Animals↗

A new series of 6-chloro-2,3-dihydro-4(1H)-quinazolinone derivatives as antiemetic and gastrointestinal motility enhancing agents.

New 6-chloro-2,3-dihydro-4(1H)-quinazolinones (24-27) have been synthesized and evaluated for gastrointestinal prokinetic and antiemetic activities in comparison with structurally related benzamides (21-22) and 6-chloro-2,3-dihydro-(1H)-1,3-benzoxazolin-4-ones (28). Their key pharmacophoric element has been defined as a 6-membered ring replacing the "virtual ring" arising from the hydrogen bond between amidic nitrogen and methoxy group in metoclopramide (1) and structurally related benzamides (2-10). Variations of heterocycle linking groups have pointed out that a lipophilic aromatic group in position 1 plays an important role for pharmacological properties, while the steric restriction and the modification of the side-chain nucleophilicity are uneffective both for the in vitro and in vivo activity. Some of these compounds very effectively enhance gut peristaltic activity in vitro (rabbit jejunum), increase gastric emptying of a semisolid meal (in rats), and inhibit cisplatin-induced emesis (in pigeons), favourably comparing with cisapride.

Animals↗