Potentiation of Glibenclamide Hypoglycaemia in Mice by MK-467, a Peripherally Acting Alpha2-Adrenoceptor Antagonist.

Pharmacological antagonism and genetic depletion of pancreatic α2A-adrenoceptors increase insulin secretion in mice and enhance the insulinotropic action of glibenclamide, a representative of the sulphonylurea class of insulin secretagogues used in the therapy of type 2 diabetes. Antagonism of α2-adrenoceptors in the central nervous system (CNS) causes tachycardia and hypertension, making generalized α2-adrenoceptor blockade unfavourable for clinical use despite its potential to decrease blood glucose levels. The purpose of this study was to test the acute effects of the peripherally acting α2-adrenoceptor antagonist MK-467 alone and in combination with glibenclamide in non-diabetic C57BL/6N mice.

Development of a hypoallergenic recombinant parvalbumin for first-in-man subcutaneous immunotherapy of fish allergy.

Background: The FAST (food allergy-specific immunotherapy) project aims at developing safe and effective subcutaneous immunotherapy for fish allergy, using recombinant hypoallergenic carp parvalbumin, Cyp c 1.

Objectives: Preclinical characterization and good manufacturing practice (GMP) production of mutant Cyp (mCyp) c 1.

Methods: Escherichia coli-produced mCyp c 1 was purified using standard chromatographic techniques.

Plasma drug concentrations and clinical effects of a peripheral alpha-2-adrenoceptor antagonist, MK-467, in horses sedated with detomidine.

Objective: To investigate plasma drug concentrations and the effect of MK-467 (L-659'066) on sedation, heart rate and gut motility in horses sedated with intravenous (IV) detomidine.

Study Design: Experimental randomized blinded crossover study.

Animals: Six healthy horses.

Influence of MK-467, a peripherally acting α2-adrenoceptor antagonist on the disposition of intravenous dexmedetomidine in dogs.

Growing evidence supports the use of (2R-trans)-N-(2-(1,3,4,7,12b-hexahydro-2'-oxo-spiro(2H-benzofuro(2,3-a)quinolizine-2,4'-imidazolidin)-3'-yl)ethyl) methanesulfonamide (MK-467), a peripherally acting α(2)-adrenoceptor antagonist, in conjunction with the sedative-anesthetic agent dexmedetomidine in animals to avoid hemodynamic compromise. We evaluated the possible effects of different doses of MK-467 on the plasma concentrations of dexmedetomidine in eight beagle dogs. Both drugs were administered intravenously.