Bioavailability of dalargin and its metabolism during intranasal administration to rats

Bioavailability and metabolism of a peptide drug Dalargin with a chemical structure Tyr-D-Ala-Gly-Phe-Leu-Arg have been examined. Dalargin is applied for the treatment of gastric and duodenal ulcers. Bioavailability was estimated following intramuscular (i/m) and intranasal (i/n) routes of administration of 3H-dalargin in anesthetized dogs. The highest dalargin concentration was achieved about 10 min after i/m and i/n administration. Absolute dalargin bioavailability was 15% and 8%, while its elimination half-life was 23.2 min and 21.3 min, respectively. Tyrosine, N-terminated tetra- and pentapeptides were the main metabolites detected in the blood. The intranasal route of dalargin administration is concluded to be possible in the clinical practice.     

Study of xanthine oxidase activity in the brain tissue after administration of dalargin during myoplegia

Effect of Dalargin (40 micrograms/kg) on xanthine-oxidase (X) activity in experimental Arduan-induced myoplegia (0.1 mg/kg) was studied in the brain tissue of 70 rats under inhalation anesthesia and artificial ventilation. Neither Dalargin nor Arduan was found separately to induce statistically significant changes in X activity. Dalargin injections in myoplegia caused significant (24.7%) reduction of the enzyme's activity.     

Role of the pituitary-adrenal system in mechanism regulating vascular permeability during stress

Disturbances of the microvascular permeability were studied by the "vascular labelling" technique during the immobilization stress of hypophysectomized and adrenalectomized rats. Animals with sham operations served as controls. As revealed, hypophysectomy and adrenalectomy caused disturbances of vascular permeability in the mesentery. Vascular permeability disturbances in the hypophysectomized and adrenalectomized rats under conditions of immobilization were more expressed than in the sham-operated animals. Removal of the pituitary and adrenal glands produced mast cell degranulation at the earlier immobilization period.     

Beneficial actions of nalorphine during hemorrhagic shock in cats

Endogenous opiates have been reported to have detrimental effects on the circulatory system during hemorrhagic shock. However, the specific opiate receptor subtype which mediates these actions has not been defined. In the present study, we have utilized the mixed agonist/antagonist, nalorphine (N-allylnormorphine), which exhibits kappa (kappa) and sigma (sigma) receptor agonism as well as mu (mu) receptor antagonism, to investigate the role of the mu receptor in hemorrhagic shock. Nalorphine (2 mg/kg) produced no significant changes in any observed experimental variable in sham-shocked animals. Shocked animals treated with nalorphine (2 mg/kg) maintained significantly higher final mean arterial blood pressures (MABP) than animals which received only vehicle (102 +/- 3.8 vs 61 +/- 6.6 mm Hg, respectively, p less than 0.001). In addition, nalorphine significantly reduced the rise in plasma MDF activity observed in untreated hemorrhaged animals (42 +/- 3.0 vs 59 +/- 4 U/ml, p less than 0.02). Our results support a significant role for the mu receptor in the deleterious actions of endogenous opioids during hemorrhagic shock.     

Effects of dalargin on hemodynamics of anesthesized rats during truncal vagotomy

I/v dalargin injection (20-25 g/kg) to narcotized rats in case of total myoplegia effectively protect hemodynamic changes under nociceptive stimulation. Bilateral truncal vagotomy partially decrease the protective effect of dalargin. Protective effect of the medicine results in activation of central and peripheral opioid receptors.