[4-proline, 8-isoleucine]-oxytocin and [4-leucine, 8-isoleucine]-oxytocin,possible intermediates in the evolutionary series of neurohypophysial hormones: Synthesis and some pharmacological properties

Zusammenfassung [4-Prolin, 8-Isoleucin]-Oxytocin und [4-Leucin, 8-Isoleucin]-Oxytocin wurden als mögliche Glieder in der entwicklungsgeschichtlichen Reihe der Neurohypophysenhormone synthetisiert und pharmakologisch geprüft.     

The synthesis and some pharmacological effects of serine4-isoleucine8-oxytocin,a probable neurohypophysial hormone

Zusammenfassung Ser⁴-Ile⁸-oxytocin wurde synthetisiert und in einer Anzahl pharmakologischer Teste geprüft. Dieses synthetische Peptid zeigt relativ hohe oxytocinartige und sehr geringe vasopressinartige Aktivitäten. Die Befunde sind vereinbar mit der Annahme, dass Ser⁴-Ile⁸-oxytocin das oxytocinähnliche Hormon der Hypophyse von Knochenfischen sein könnte.     

Biological properties of synthetic Ser4-Arg8-oxytocin (Ile3-Ser4-Arginine vasopressin): Role of the residue No. 4 in the hormone-pressor receptor interaction

Résumé Les propriétés pharmacologiques de la Ser⁴-Arg⁸-ocytocine (Ser⁴-vasotocine) synthétique ont été étudiées. La substitution en position 4 de la glutamine par la sérine diminue considérablement l'activité pressique de la vasotocine, ce qui montre l'importance de cette position dans les interactions entre les hormones neurohypophysaires et le récepteur vasopressique.

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The authors are indebted to Dr.Albert Jöhl (Ciba-Geigy Laboratories) for a sample of synthetic Ser⁴-Arg⁸-oxytocin. They thank Mrs.Christine Gaullier for ther skilled technical assistance.     

Effects of ornithine8-oxytocin and ornithine8-vasopressin on the permeability of toad skin

Résumé En employant des crapauds pour doser l'action des peptides sur la perméabilité de la peau, l'effet hydrosmotique de l'arginine⁸-vasotocine s'est montré 200 fois plus puissant que celui de l'ornithine⁸-oxytocine. Ce fait confirme l'importance hydrosmotique de l'acide aminé arginine dans la position 8. Tous 2 ont eu un effet natriférique, mais ce ne fut pas le cas de la lysine⁸-vasopressine et l'ornithine⁸-vasopressine. L'importance natriférique de l'acide aminé isoleucine dans la position 3 en est confirmée.     

Inactivation of deamino-oxytocin,deamino-carba1-oxytocin, [D-Lys8]-, and [D-Arg8]vasopressins by kidney cell particles

Zusammenfassung Die Inaktivierung von Carba-, Deamino- und 8-d-substituierten Analogen der neurohypophysäuren Hormone durch Schweinenierenhomogenate verläuft mit der gleichen Geschwindigkeit wie die des Oxytocins und Vasopressins.     

Über Peptidsynthesen,XLIV. Synthese von Ser4-Glu(NH2)8-Oxytocin (Glumitocin)

Summary Ser⁴-Glu(NH₂)⁸-Oxytocin has been synthesized. The identity of the synthetic compound with the neurohypophysal hormone (Glumitocin) recently isolated from species of cartilaginous is demonstrated.

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Über Peptidsynthesen XLIII. Mitteilung,E. Klieger, Experientia23, 620 (1967).     

2-o-Iodotyrosine]-oxytocin and [2-o-methyltyrosine]-oxytocin: basic pharmacology and comments on their potential use in binding studies

Both [2-o-iodotyrosine]-oxytocin and [2-o-methyltyrosine]-oxytocin display only weak vasopressor and antidiuretic effects on rats. They inhibit the in vitro uterotonic action of oxytocin; this inhibition is not fully competitive. It is concluded that they are not suitable as markers for studies of uterine receptor for oxytocin.     

Solid phase synthesis and some pharmacoogical properties of 4-Ser-8-Gln-Oxytocin (Glumitocin)

Zusammenfassung Eine neue Synthese des Peptidhormons Glumitocin wird beschrieben, in der die Trägermethode vonMerrifield benutzt wird. Einige pharmakologische Daten des Hormons werden mitgeteilt.

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This work was supported in part by a grant from the Medical Research Council of Canada, Banting Research Foundation, National Science Foundation Grant No. GB 4932X and a General Research Support Grant from the National Institutes of Health.     

[2-o-Iodotyrosine]-oxytocin and [2-o-methyltyrosine]-oxytocin: Basic pharmacology and comments on their potential use in binding studies

Summary Both [2-o-iodotyrosine]-oxytocin and [2-o-methyltyrosine]-oxytocin display only weak vasopressor and antidiuretic effects on rats. They inhibit the in vitro uterotonic action of oxytocin; this inhibition is not fully competitive. It is concluded that they are not suitable as markers for studies of uterine receptor for oxytocin.Supported by the Swiss National Science Foundation, grant No. 3.2080.73.Deceased 30 April 1975.     

The deamino derivatives of [4-threonine]-oxytocin and [4-threonine]-mesotocin; Analogs possessing a surprising spectrum of diminished pharmacological activities

Zusammenfassung Synthese (Merrifield-Methode) und pharmakologische Eigenschaften der Desamino-Derivate von (4-Threonin)-Oxytocin und (4-Threonin)-Mesoxytocin werden beschrieben.

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This work was supported in part by the Medical College of Ohio, a Contract (No. 69-2193) from the Center for Population Research of the National Institute of Child Health and Human Development, Research Grants from the National Science Foundation (No. GB-4932), the National Institute of Arthritis and Metabolic Diseases (No. AM-01940) and a General Research Support Grant to Columbia University from the National Institutes of Health. The authors wish to thank Mrs.Sara Crumm for performing the amino acid analyses and Mrs.Margot Acosta for performing the bioassays. An abstract of part of this work was presented at the 2nd American Peptide Symposium, Cleveland, Ohio, August 1970;M. Manning andW. H. Sawyer,Peptides (Ed.Saul Lande, Gordon and Breach, New York 1971), in press.     

The influence of sodium-8-chlorotheophyllinate (S8CT) on immune processes

Summary S8CT injected at the time of immunization significantly enhances specific IgM-production but has no effect on IgG-formation. Mitogen (PHA-P) induced macrophage migration inhibition of cells of S8CT pretreated animals is reduced. The same effect is observed, when normal cells are tested in the presence of S8CT in vitro. Blast transformation of B-lymphocytes but not of thymocytes is significantly stimulated by S8CT. Acid phosphatase activity is also stimulated in B-cells and- to a lesser degree-in cortisone-resistant T-lymphocytes whereas the activity of the total thymocyte population is reduced. No effect was seen on phagocytosis and intracellular bactericidal activity. A stimulatory effect of S8CT for B-cells is postulated.Presented in part at the Xth International Congress of Allergology and Clinical Immunology, Jerusalem/Israel 1979, Nov. 4–11.     

The efficacy of a novel compound, (E)-1-(4′-bromo-4-biphenylyl)-1-(4-chlorophenyl)-3-dimethylaminoprop-1-ene againstTrypanosoma cruzi in mice

Summary The biological properties of a novel compound 353C with high activity againstTrypanosoma cruzi, are described. The compound was about 10 times and 20 times more effective than either benznidazole or nifurtimox respectively, in producing radical cure in mice. 353C had a long half-life and showed anti-trypanosomal properties when given to mice at weekly intervals.     

Antihypertensive and other cardiovascular effects of 2-(3-pyridyl)- and 2-(4-pyridyl)-4-trifluoromethylimidazoles

Summary 2 new 4-trifluoromethylimidazole derivatives were found which lowered mean arterial pressure in renal and spontaneously hypertensive (SH) rats by the oral route. In SH rats, compounds A and B were 0.1 and 0.3 times, respectively, as potent as hydralazine. No tolerance development was observed in SH rats with either compound over a 1-week period. In anesthetized dogs, both compounds lowered arterial pressure and peripheral vascular resistance but increased cardiac output. By intraarterial administration, both compounds increased femoral arterial blood flow. These findings represent discovery of a new class of vasodilator drugs.Deceased, May 31, 1978.