ABSTRACT
Synthesis of four new N,N-disubstituted derivatives of enkephalin analogs: All2Tyr-DMet-Gly-Phe-epsilon Ahx-OMe 5, Bu2Tyr-DMet-Gly-Phe-epsilon Ahx-OMe 6, All2Tyr-DMet-Gly-Phe-epsilon Ahx-epsilon Ahx-OMe 11 and Bu2Tyr-DMet-Gly-Phe-epsilon Ahx-epsilon Ahx-OMe 12 is reported. they were tested for agonistic and antagonistic activity. Compound 5 is a little more potent agonist (IC50 = 1.9 x 10(-7) M/l, GPI) than compound 6(IC50 = 7.2 x 10(-7) M/l, GPI). They both are highly selective to mu receptor, because they show no trace of activity to delta receptor in concentration up to 10(-5) M/l. Compound 11 and 12 are less active and not selective as agonists. None of these compounds showed antagonistic activity.
Subject(s)
Enkephalins/chemical synthesis , Amino Acid Sequence , Animals , Chromatography, High Pressure Liquid , Enkephalins/pharmacology , Guinea Pigs , Ileum/drug effects , In Vitro Techniques , Magnetic Resonance Spectroscopy , Male , Mice , Molecular Sequence Data , Morphine/pharmacology , Muscle, Smooth/drug effects , Vas Deferens/drug effectsABSTRACT
Synthesis of four new derivatives of enkephalin analogs: H-BuTyr-DMet-Gly- Phe-epsilon Ahx-OH 9, H-BzlTyr-DMet-Gly-Phe-epsilon Ahx-OH 12, H-Butyr-DMet-Gly- -Phe-epsilon Ahx-epsilon Ahx-OH 15 and H-BzlTyr-DMet-Gly-Phe-epsilon Ahx-OH is reported. They were examined for agonistic, antagonistic and analgesic activity. Compound 12 is the most potent among investigated peptides. Its agonistic activity in vitro is 7.85 x 10(-8) M/l (GPI) and 9.5 x 10(-7) M/l (MVD). None of the peptides showed antagonistic activity. Only compound 12 showed weak, not dose-dependent analgesic activity in rats.
Subject(s)
Enkephalins/chemical synthesis , Amino Acid Sequence , Amino Acids/analysis , Animals , Chromatography, High Pressure Liquid , Enkephalins/chemistry , Guinea Pigs , In Vitro Techniques , Magnetic Resonance Spectroscopy , Male , Mice , Molecular Sequence Data , Morphine/antagonists & inhibitors , Morphine/pharmacology , Naloxone/pharmacology , Rats , Rats, Inbred Strains , Receptors, Opioid/drug effects , Receptors, Opioid/metabolismABSTRACT
The synthesis of two new angiotensin II analogs: [Des-Arg2, epsilon Ahx1]-angiotensin (II (1) and [Des-His0)-angiotensin (II (2) is reported. Rather strong agonist activity shows analog (1)-78% and weak-analog (2)-30% of the contractile activity of angiotensinamide. None of the synthesized peptides has antagonist activity.
Subject(s)
Angiotensin II/analogs & derivatives , Vasoconstrictor Agents/chemical synthesis , Animals , Male , Muscle, Smooth, Vascular/drug effects , Rats , Rats, Inbred Strains , Vasoconstriction/drug effects , Vasoconstrictor Agents/pharmacologyABSTRACT
The authors report three cases of central nervous system cryptococcosis in children in the first decade of life, from Rio Grande do Sul State, Brazil. Diagnosis was supported by demonstration of Cryptococcus neoformans with India-ink preparations of the spinal fluid and Sabouraud's media culture. Clinical presentation included acute, subacute and chronic forms. Increased intracranial pressure and hydrocephalus were the complications during the course of the disease, and a ventriculoperitoneal shunt was used in one case. Undernutrition was associated with all cases and tubercle bacillus infection with one. Specific therapy was administered to the three patients. One patient was cured and the other two died.
