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Biomedical subjects

A Barnett

Publications and source records attributed to A Barnett.

At least 127 records · Page 7Linked to original sources
PubMed1984

Gastric antisecretory properties of SCH 32651.

This report describes the gastric antisecretory properties of SCH 32651 (3-amino-2-methyl-8-phenylmethoxyimidazo[1,2-a] pyrazine HCl . 1/3 H2O). In the pyloric ligated rat, SCH 32651 inhibited gastric acid secretion; the oral ID50 (95% confidence limits) was 23.7 (13.8-39.2) mg/kg. In Heidenhain pouch dogs, SCH 32651 antagonized histamine-stimulated acid secretion with an ID50 of 1.44 (0.55-3.91) mg/kg p.o. SCH 32651 was also active against secretory responses to dimaprit, pentagastrin and feeding in dogs. In all test models SCH 32651 showed similar potency to cimetidine. Chronic administration of SCH 32651 or cimetidine caused slight tolerance and its antisecretory effect was readily reversible on cessation of dosing. The data indicate that SCH 32651 is an orally effective novel antisecretory drug.

Administration, Oral↗
PubMed1984

Gastric cytoprotective properties of SCH 32651, a novel antiulcer agent.

The antisecretory activity of SCH 32651 (3-amino-2-methyl-8-phenylmethoxyimidazo[1,2-a] pyrazine HCl . 1/3 H2O) has been described in a preceding paper. This report describes its gastric cytoprotective properties. SCH 32651 inhibited the gastric lesions due to ethanol in a dose-dependent manner (ID50 = 5 mg/kg p.o.) and exerted its maximal effect when given 30 min before ethanol and had a duration of at least 90 min at 30 mg/kg p.o. The activity of SCH 32651 against ethanol was unaffected by indomethacin pretreatment. Furthermore, SCH 32651 produced significant increases in gastric mucus release (10-100 mg/kg p.o.) and rapidly reversed ethanol-induced (30-100 mg/kg p.o.) fall in gastric potential difference (PD). SCH 32651 displayed significant antiulcer activity in indomethacin-(30-100 mg/kg p.o.), aspirin - (30-100 mg/kg p.o.), "aspirin + acid" - (10-100 mg/kg p.o.), reserpine - (10-100 mg/kg p.o.), stress - (30-100 mg/kg p.o.), and cysteamine (10-100 mg/kg p.o.) ulcers. The present data in conjunction with those reported in a preceding paper indicate that SCH 32651 is an orally effective novel antiulcer drug with both gastric antisecretory and cytoprotective properties.

Administration, Oral↗
PubMed1984

Effects of a gastric antisecretory-cytoprotectant 2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine-3-acetonitrile (Sch 28 080) on cysteamine, reserpine and stress ulcers in rats.

Prostaglandin E2 and carbenoxolone, putative cytoprotective agents, were tested in cysteamine, reserpine and stress ulcers in rats. In cysteamine-induced duodenal ulcer, PGE2 was inactive at 0.1 and 0.5 mg/kg p.o.; carbenoxolone at 100 mg/kg p.o. decreased the incidence but not the severity of the ulcer. PGE2 at 5.0 mg/kg p.o. and carbenoxolone at 300 mg/kg p.o. showed moderate effects, but the dosage also inhibited cysteamine-stimulated acid secretion. PGE2 (0.1 and 0.3 mg/kg p.o.) was inactive and carbenoxolone (100 and 300 mg/kg p.o.) further aggravated the gastric ulceration caused by reserpine or cold-restraint stress. In contrast, atropine (3 and 10 mg/kg p.o.) and cimetidine (30, 100 and 300 mg/kg p.o.) were active in all three ulcer models. But the results with cimetidine in stress ulcer were somewhat variable. 2-methyl-8-(phenylmethoxy) imidazo [1,2-a] pyridine-3-acetonitrile (Sch 28 080), a novel structure with both cytoprotective and antisecretory activity, was highly efficacious in cysteamine, reserpine and stress ulcers (1-30 mg/kg p.o.), which was presumably adequately accounted for by its potent antisecretory activity. It is concluded that cysteamine, reserpine and stress ulcers may not be appropriate models for testing the potential antiulcer effect of primarily cytoprotective compounds.

Animals↗
PubMed1983

Comparison of synthetic adhesive moisture vapor permeable and fine mesh gauze dressings for split-thickness skin graft donor sites.

SAM and fine mesh gauze dressings were compared on 60 consecutive skin graft donor sites. SAM dressings are significantly better than fine mesh gauze dressings for healing of split-thickness skin graft donor sites; healing occurs much more rapidly with much less pain. In patients known to be colonized with Pseudomonas, care should be taken when using SAM dressings, although it is not an absolute contraindication. There were no clinically significant differences between Tegaderm and Op-Site.

Adolescent↗
PubMed1983

Effects of selected drugs on spontaneously occurring abnormal behavior in beagles.

A sub-population of beagles with abnormal behavioral patterns has been identified, isolated and tested for responsively to selected classes of psychoactive drugs. The abnormal behavior was ameliorated by anxiolytics and antidepressants but not by antipsychotics, an antihistaminic, an alpha-adrenergic blocker, a beta-adrenergic blocker, or an anticholinergic drug. Improvement occurred after a single dose of the anxiolytic drugs but did not occur until 10-18 days after daily dosing with standard tricylic antidepressants and the MAO inhibitor isocarboxazid. This delayed onset in beagles resembles that seen on use of these drugs in humans. The results with these drugs suggest that the abnormal behaviors of the beagles are related to anxiety and are in part depressive in nature. This colony provides an animal model of abnormal behavior which allows evaluation of the anxiolytic and antidepressant effects of drugs and estimates of the onset of action of antidepressant drugs.

Amobarbital↗
PubMed1983

Determination of analgesic drug efficacies by modification of the Randall and Selitto rat yeast paw test.

This report describes a modified Randall and Selitto (1957) rat yeast paw test that can evaluate differences in efficacy of different analgesics. The modifications consist of a decrease in the rate of acceleration of the noxious stimulus (mechanical pressure) on the inflamed paw from 20 to 12.5 mmHg/sec and an extension of the cut-off time from 15 to 60 sec. All the narcoticlike drugs tested (morphine, codeine, and pentazocine) increased the response latencies of the inflamed paws to the cut-off time. The nonsteroidal antiinflammatory-like drugs tested (acetylsalicylic acid, acetaminophen, indomethacin, phenylbutazone, and proquazone) showed plateaus in their analgesic effects (i.e., increasing the dose failed to produce significantly greater increases in the response latencies compared to the next lower dose). Zomepirac (80-240 mg/kg p.o.) did not show this plateau effect, but was unable to increase response latencies to greater than 30 sec because of the toxicity of higher doses (320 mg/kg p.o.). Flunixin NMG (the meglumine salt of flunixin), a nonnarcotic analgesic, did not display a plateau effect and increased response latencies to maximum values. The methodology was therefore able to discriminate analgesics active against mild to severe clinical pain (narcoticlike) from those only useful against mild to moderate pain (nonnarcotic-like).

Analgesics↗
PubMed1983

Leg muscle pH following sprint running.

In an effort to compare the disturbances in leg muscle pH during sprint running, muscle biopsies were obtained from the gastrocnemius and vastus lateralis muscles of six healthy men (three endurance-trained and three nonendurance-trained) before and after a treadmill sprint run (TSR) to fatigue (54-105 s) at roughly 125% of their aerobic capacities. Following the TSR, repeated blood samples were taken from a hand vein and later analyzed for pH, PCO2, and lactic acid (HLa). The muscle specimens were analyzed in duplicate for pH and HLa. Resting-muscle pH was 7.03 +/- 0.02 (means +/- SE) and 7.04 +/- 0.01 for the gastrocnemius and vastus lateralis muscles, respectively. At the termination of the TSR, the pH in these muscles was 6.88 +/- 0.05 and 6.86 +/- 0.03, respectively. After a 400-m timed run on the track, the pH in the gastrocnemius of four of the subjects averaged 6.63 +/- 0.03, while blood pH and HLa were 7.10 +/- 0.03 and 12.3 mM, respectively. Although no differences in pH and HLa were observed between the vastus lateralis and gastrocnemius muscles at the end of the treadmill trial, it is speculated that the lesser disturbance in acid-base balance seen in endurance performers may have been due to a lesser production of metabolites in their running musculature when compared to nonendurance performers.

Adult↗
PubMed1983

SCH 23390, a potential benzazepine antipsychotic with unique interactions on dopaminergic systems.

SCH 23390 [R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol) possesses pharmacologic effects similar to standard antipsychotics, including selective supression of conditioned avoidance responding in rats and squirrel monkeys, blockade of apomorphine-induced stereotypy in rats and blockade of methamphetamine-induced lethality in aggregated mice. At effective doses in these tests, no changes in gross behavior, neurological or autonomic function were observed. In contrast to the standards tested, SCH 23390 blocked dopamine-stimulated adenylate cyclase at concentrations (IC50 = 0.01 microM) about 2000 times lower than those needed to block spiperone binding (IC50 = 24 microM). This suggests specific D1-receptor antagonism. Inability of SCH 23390 to cause hyperprolactinemia, considered to be a D2-receptor effect, is consistent with this hypothesis. SCH 23390 showed lower increases in dopamine turnover suggesting that the blockade of SCH 23390 may be more specific for post- than presynaptic sites. Additional evidence for the selectivity of SCH 23390 among putative postsynaptic dopamine sites includes its lack of effect on apomorphine-induced hypothermia or emesis. Based on these results, it is postulated that SCH 23390 is a selective D1-receptor antagonist.

Animals↗
PubMed1983

Studies on the mechanisms of the antisecretory and cytoprotective actions of SCH 28080.

The antisecretory and cytoprotective actions of SCH 28080 (2-methyl-8-(phenylmethoxy)imidazol[ 1,2-a ]pyridine-3-acetonitrile), an antiulcer compound, were characterized. In the isolated guinea-pig gastric mucosa, SCH 28080 at 5 X 10(-8) M abolished the acid secretory responses to histamine and methacholine but at 5 X 10(-7) M also inhibited the responses to dibutyryl cyclic AMP plus theophylline. The data suggest that the antisecretory effect of SCH 28080 involves a direct action on the parietal cells distal to the primary events mediating the cholinergic and H2 histaminergic secretory mechanisms. In the histamine-stimulated dogs, a prolonged suppression of acid secretion was accompanied by only a transient fall in the ratio of mucosal plasma flow to acid output after i.v. dosing of SCH 28080, 1 mg/kg, indicating that the antisecretory action of SCH 28080 was not secondary to changes in gastric blood flow. Mechanisms mediating the cytoprotective effects of SCH 28080 were investigated. SCH 28080 (10 mg/kg p.o.) increased total mucus as determined by measurements of N-acetylneuraminic acid in rat stomach. In the isolated guinea-pig gastric mucosa, bicarbonate secretion was augmented in a dose-dependent (10(-6)-10(-4) M) manner. Concomitant stimulation of the gastric mucus and bicarbonate by SCH 28080 may lead to strengthening of the gastric mucosal barrier and account for its gastric cytoprotective activity against injuring agents. In conclusion, the antisecretory and cytoprotective activities of SCH 28080 are due to a direct action on the parietal cells and a stimulatory effect on mucus and bicarbonate secretion by the mucosal epithelial cells, respectively.

Animals↗
PubMed1983

Scalp as skin graft donor site: rapid reuse with synthetic adhesive moisture vapor permeable dressings.

Synthetic Adhesive Moisture vapor permeable (S.A.M.) dressings, Op-Site and Tegaderm, are compared to Fine Mesh Gauze (F.M.G.), as a dressing for split-thickness skin graft donor sites. Scalp as a donor site is compared to nonscalp donor sites. The combination of S.A.M. dressings and scalp as a donor site allows for rapid reuse of a donor site. Pain is substantially decreased and rate of healing is increased when this combination is used. The scalp, because of its availability, accessibility, excellent color match for facial grafting, and rapid healing, is recommended as a donor site.

Adhesives↗
PubMed1982

Potentiation of [D-ala2]enkephalinamide analgesia in rats by thiorphan.

The effect of thiorphan, an inhibitor of enkephalin dipeptidyl carboxypeptidase, was tested in the rat tail-flick test. When given alone up to 100 mg/kg s.c., thiorphan had no effect. However, thiorphan (30 mg/kg, s.c.) potentiated intraventricularly administered [D-Ala2,Met5]enkephalinamide (DEAEM) and its [Leu5]-derivative, whereas it had no effect on [D-Ala2,Met5]enkephalin, [D-Met2,Pro5]enkephalinamide, or morphine. Potentiation of DAEAM by thiorphan was dose-responsive and naloxone reversible. The most efficient enhancement of the analgesic effects of DAEAM was seen when the two drugs were co-administrated in rapid succession. Thus, thiorphan potentiation of opioid-peptide induced analgesia in the rat is similar to that seen in the mouse.

Amino Acids, Sulfur↗
PubMed1982

The sedative-hypnotic properties of quazepam, a new hypnotic agent.

7-Chloro-1-(2,2,2-trifluoroethyl)-5-(o-fluorophenyl)-1,3-dihydro-2H-1, 4-benzodiazepine-2-thione (Sch 16134, quazepam) is a new hypnotic drug with demonstrated clinical efficacy. Quazepam has been shown in our laboratories to have potent hypnotic activity and fewer side effects at effective doses than flurazepam, which was studied concurrently. Hypnotic potency was estimated in mice via antagonism of electroshock-induced convulsions (ECS), potentiation of hexobarbital-induced sleeping time, and chlorprothixene potentiation. The respective oral ED50's (95% fiducial limits) in the 3 tests were 0.9 (0.4-2.0), 0.5 (0.3-0.8) and 0.05 (0.02-0.08) mg/kg for quazepam and 1.6 (1.1-2.3), 0.6 (0.4-1.0) and 0.11 (0.07-0.42) mg/kg for flurazepam. The duration of action of quazepam as measured by antagonism of ECS in mice was similar to that of flurazepam at equi-effective doses but quazepam had a faster onset. When potential tolerance to hypnotic efficacy was studied, quazepam did not show tolerance after dosing 20 mg/kg p.o. twice daily (b.i.d.) for 5 days, whereas tolerance was seen with flurazepam at equi-effective doses b.i.d. for 5 days. In conscious, unrestrained squirrel monkeys and cats, quazepam produced sedation with less ataxia and less evidence of CNS stimulant action than flurazepam. On the basis of the aforementioned studies, quazepam should be an effective hypnotic with less potential for ataxia, paradoxical excitation, and tolerance than flurazepam.

Animals↗
PubMed1982

Pharmacological studies with quazepam, a new benzodiazepine hypnotic.

7-Chloro-1-(2,2,2-trifluoroethyl)-5-(o-fluorophenyl)-1, 3-dihydro-2H-1,4-benzodiazepine-2-thione (Sch 16134, quazepam) demonstrated high safety and effective hypnotic properties. Toxicity of quazepam in mice was extremely low at the largest doses administered of 5000 mg/kg p.o. and 1370 mg/kg i.p. as compared to LD50 values for flurazepam of 756 (635-889) mg/kg p.o. and 254 (234-280) mg/kg i.p. In cats, quazepam did not produce overt toxicity even at the highest dose administered, 1000 mg/kg p.o., whereas death occurred after the administration of flurazepam at a median dose of 250 mg/kg p.o. In addition, flurazepam produced central excitation and convulsions. Quazepam did not affect hemodynamic parameters in conscious dogs and anesthetized cats. Autonomic functions were virtually unaffected by the drug in anesthetized cats. In interaction studies in mice, quazepam did not interact with cimetidine while it potentiated the sedative activity of alpha-methyldopa, ethanol and propranolol. The CNS depressant properties of quazepam were further investigated by studying its effects on spontaneous motor activity in mice and EEG pattern in immobilized cats. In mice, quazepam reduced locomotor activity at doses which did not impair motor coordination thus differing from flurazepam which did. In the EEG study, quazepam produced a slow wave EEG pattern comparable to that of physiological sleep, while flurazepam induced a similar EEG activity which alternated with a fast frequency pattern of moderate amplitude. Quazepam also showed potent anticonvulsant activity. These results suggest that quazepam is likely to be a safe and effective sleep-promoting agent.

Animals↗