Disease relevance of DEVAZEPIDE

• In contrast to its effects on morphine analgesia, devazepide had no effect on the various indices of morphine-induced respiratory depression [1].
• 3. Both the pressor response and bradycardia elicited by sCCK-8 were reduced by the selective CCKA receptor antagonists, devazepide (0.5-50 nmol kg-1) and lorglumide (1-7 mumol kg-1) [2].
• Intrathecal administration of the selective CCKB receptor antagonist L-365260 dose-dependently inhibited neurotensin hyperalgesia from the RMg (ID50 = 0.42 ng) at doses approximately 1000-fold less than that observed with the selective CCKA receptor antagonist devazepide (ID50 = 646 ng) [3].
• Enhancement of the cytotoxicity of cisplatin by the cholecystokinin antagonist MK-329 in a human pancreatic cancer cell line [4].
• Intraperitoneal injection of 100 micrograms devazepide/kg body weight prevented this effect [5].

Psychiatry related information on DEVAZEPIDE

• However, the concomitant treatment of CCK-8 with L-365,260 and proglumide, differently from devazepide, also suppressed the locomotor activity in the open-field test [6].
• 1. The effect of the CCKA receptor antagonist, devazepide (100 mg kg-1) on meal parameters during the initial phase of the dark period was studied in free-feeding rats by use of a procedure for continuously monitoring feeding patterns [7].
• Effect of intracerebroventricular and systemic injections of caerulein, a CCK analogue, on electrical self-stimulation and its interaction with the CCKA receptor antagonist, L-364,718 (MK-329) [8].
• The possible effect of a cholecystokinin-8 agonist (caerulein) and antagonists (MK-329 and L365,260) on the development of morphine dependence and withdrawal were investigated in rats [9].
• Neither the 3S-(-) enantiomer of L-365,260 nor devazepide (both administered at 100-10,000 micrograms.kg-1) enhanced the exploratory behavior of mice [10].

High impact information on DEVAZEPIDE

• This effect was reversed by prior treatment with MK-329, a selective antagonist of CCK at alimentary-type CCK (CCK-A) receptors [11].
• Effects of a novel cholecystokinin (CCK) receptor antagonist, MK-329, on gallbladder contraction and gastric emptying in humans. Implications for the physiology of CCK [12].
• L-365,260 but not devazepide inhibited the HDC activation [13].
• Moreover, pretreatment of the intraduodenal protein meal with the cholecystokinin-A receptor antagonist MK-329 abolished increases of S-28 and S-14 and caused a further twofold increase of gastric acid (P < 0.025) [14].
• Gastric emptying rate was significantly accelerated by MK-329 during the initial 75 minutes after the meal, but the time for 50% emptying did not differ from placebo [127.5 +/- 7.7 vs. 140.0 +/- 9.0 minutes (NS)] [15].

Chemical compound and disease context of DEVAZEPIDE

• Pretreatment with devazepide receptor (1 microgram/kg) antagonized the inhibitory effects of buspirone and 8-OH-DPAT injected i.p. on emotional stress-induced colonic hyperkinesia but did not alter the effects of clonazepam (1 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)[16]
• Half of the rats (DEV group) were pretreated with devazepide (300 microg/kg body weight) and the other half (CON group) with vehicle, 30 min prior to CS training sessions and choice tests [17].
• In experiment 1, 15 min of sucrose intake in adult, male Sprague-Dawley rats after 6 h of food deprivation was increased by devazepide (20 micrograms/kg) administered into the SPD artery whether given alone or in conjunction with cholecystokinin octapeptide (CCK-8, 2 micrograms/kg ip) [18].

Biological context of DEVAZEPIDE

• The decrease in food intake which occurs 5 hr after i.p. injection of leptin alone was also blunted by devazepide [19].
• Devazepide and proglumide were, respectively, the most and the least potent inhibitors of G401 cell growth (potency order devazepide > L-365,260 = lorglumide > loxiglumide > benzotript > proglumide) [20].
• Melatonin generally enhanced the antiproliferative effects of devazepide, lorglumide and proglumide and increased the proglumide-induced apoptosis [21].
• The CCK1 receptor antagonist devazepide was a poor CCK2 receptor antagonist with an IC50 of about 800 nM [22].
• 3 Devazepide (0.5 mg kg(-1), i.v.), a selective CCK(1) receptor antagonist, blocked the effects of CCK on arterial blood pressure, heart rate and neuronal discharge but did not significantly alter these responses to PBG [23].

Anatomical context of DEVAZEPIDE

• MK-329 caused a dose-dependent inhibition of CCK-stimulated gallbladder contraction with 10 mg producing complete blockade (P less than 0.01, cf. placebo) [12].
• MK-329 has no direct effect on the pancreas [24].
• Cholecystokinin receptor antagonist MK-329 blocks intestinal fat-induced inhibition of meal-stimulated gastric acid secretion [25].
• Oral pretreatment with MK-329 (1 mg/kg) significantly reversed the inhibition of gastric acid output caused by lipid perfusion of the duodenum and jejunum, but fat-induced inhibition of gastric emptying was not significantly affected [25].
• Competition of [125I]Bolton-Hunter cholecystokinin octapeptide binding in the cortex, nucleus accumbens, caudate nucleus, hippocampus, cerebellum and brainstem was much greater in the presence of L-365,260 than devazepide, thereby suggesting that the majority of cholecystokinin receptors in these regions are of the cholecystokinin-B subtype [26].

Associations of DEVAZEPIDE with other chemical compounds

• The response to CCK was inhibited in a competitive manner by the addition of the benzodiazepine analog, MK-329 [27].
• We conclude that CCK receptor blockade with 10 mg MK-329 does not alter plasma insulin, glucagon, or glucose responses to a mixed meal [28].
• 1. Three recently described non-peptide cholecystokinin (CCK) antagonists (devazepide, lorglumide, loxiglumide) have been studied for their antagonism of the contraction to cholecystokinin-octapeptide (CCK-OP) in human alimentary muscle and guinea-pig intestine [29].
• The effect of oleate was abolished by the CCK-A receptor antagonist Devazepide (0.5 mg/kg), whereas the effect of butyrate persisted despite pretreatment with either Devazepide or a combination of the calcium channel inhibitors nifedipine (1 mg/kg) and the omega-conotoxins GVIA and SVIB (each 25 microg/kg) [30].
• 4. Previous i.c.v. injection of devazepide, a CCKA receptor antagonist, (10 micrograms kg-1) antagonized the inhibitory effects of both CCK-8s and igmesine injected i.c.v. on dopamine-induced colonic hyperkinesia.(ABSTRACT TRUNCATED AT 250 WORDS)[31]

Gene context of DEVAZEPIDE

• This paper reviews experiments in which devazepide (a selective CCK-A receptor antagonist) and L-365,260 (a selective CCK-B-gastrin receptor antagonist) have been used [32].
• Thus, devazepide, a selective CCK-A receptor antagonist, produced a dose-related inhibition of the CCK-8-stimulated rise in circulating beta-endorphin concentrations [33].
• Injected i.c.v., devazepide (L 364,718), a CCKA receptor antagonist, at 0.1 and 1 microgram/kg, abolished the effect of both JO 1784 and NPY; by contrast L365,260, a CCKB antagonist, required a dose of 10 micrograms/kg to block the antagonistic effect of NPY and JO 1784.(ABSTRACT TRUNCATED AT 250 WORDS)[34]
• MK-329, a CCK-A receptor selective antagonist, at a dose of 20 nmol/kg fully inhibited the action of 20 nmol/kg CCK8, while 100 nmol/kg of (R)L-365,260, a CCK-B selective antagonist, had no effect on the CCK8 response [35].
• In Experiments 1 and 2, pups received the selective CCK1 receptor antagonist devazepide (600 microg/kg), the selective CCK2 receptor antagonist L365,260 (600 microg/kg), or vehicle [36].

Analytical, diagnostic and therapeutic context of DEVAZEPIDE

• In a double-blind, four-period crossover study eight subjects received single doses of 0.5, 2, or 10 mg MK-329, or placebo, followed by an intravenous infusion of CCK-8 (30 pmol/kg.h) [12].
• In a double-blind, two-period, randomized crossover design, the subjects received either 10 mg MK-329 or placebo orally 3 hours 15 minutes before the meal, which contained 51CrCl3 as food marker [15].
• Treatment with MK-329 enhances morphine analgesia and chronic treatment with MK-329 prevents the development of tolerance to morphine analgesia [37].
• 3. The response to 100 pmol CCK was completely abolished by devazepide (0.5 mg kg-1) and by chronic subdiaphragmatic vagotomy performed 10-14 days prior to experimentation, indicating that CCK sensitivity was via CCKA receptors and exclusively mediated via vagal afferents rather than splanchnic or enteric afferents [38].
• The suppression of food intake by beta-conglycinin peptone was abolished by an intravenous injection of devazepide, a selective peripheral CCK receptor antagonist [39].

References