I.I.A. Tabachnick

Biological studies on an anti-androgen (SH 714)

Abstract The biological properties of the anti-androgen, SH 714 (Cyproterone acetate) were determined. This compound is strongly anti-androgenic in testosterone-stimulated, orchiectomized rats and in intact male rats when administered either subcutaneously or orally. The steroid is also androgenic, progestational, anti-estrogenic, and at high doses, possesses anti-gonadotropin activity. It is devoid of anti-inflammatory activity. SH 714 also exhibited an anti-fertility effect, probably due to its potent progestational activity. When administered to orchiectomized, testosterone-stimulated orchiectomized or intact male rats, adrenal atrophy occured, and in intact animals, this atrophy was accompanied by a decrease in plasma corticosterone levels. The adrenal effects are probably due to pituitary ACTH suppression. Hypercholesterolemia also occured in treated male rats.

The pharmacology of azatadine, a potential antiallergy drug

Azatadine (6–11-dihydro-11-[1-methyl-4-piperclylidene]-5H{5,6}cyclohepta{1,2-b}pyridine maleate {1∶2}), a nitrogen analog of cyproheptadine has been studied for its antiallergy properties. It was compared in vivo and in vitro to cyproheptadine and seven (7) standard antihistamines: chlorpheniramine, promethazine, diphenhydramine, phenindamine, chloropyriline, tripelennamine and chlorcylizine; an antiserotonin, methysergide; and an anticholinergic, atropine.Azatadine possesses potent antihistaminic, anticholinergic, antiserotinin and antianaphylactic properties. In vitro, azatadines antihistamine potency is equal to chlorpheniramine, cyproheptadine, phenindamine, chloropyrilene and greater than the rest of the antihistamines studied. Its anticholinergic potency is 1/3 that of atropine, equal to promethazine and cyproheptadine and greater than the rest of the antihistamines studied. Its antiserotonin potency is 1/4 that of methysergide, equal to promethazine and greater than the rest of antihistamines studied.In vivo, azatadines ability to protect guinea-pigs from histamine lethality (i.v.) and histamine-induced dyspnea is greater than all of the antihistamines studied. Its ability to protect guinea-pigs from acetylcholine-induced dyspnea is equal to atropine and greater than all of the antihistamines studied. Its ability to protect guinea-pigs from serotonin-induced dyspnea is 1/6 that of cyproheptadine, 1/8 that of methysergide and greater than all of the antihistamines studied.Azatadine is a more potent antianaphylactic agent and has greater therapeutic indices than cyproheptadine in both mice and guinea-pigs.

The hyperglycemic activity of benzothiadiazine and other diuretics

Abstract Considerable evidence is available which demontrates the tendency of certain benzothiadiazine diuretics to elevate blood glucose values in seemingly normal, as well as diabetic or pre-diabetic, individuals (1–5). A recent review (5) concerning the benzothiadiazine diuretics suggest that the hyperglycemic potential of all members of this chemical class is equivalent to their diuretic potency. The paucity of data encouraged us to determine systematically the degree of hyperglycemia elicited in rats by eleven benzothiadiazine diuretics. Chlorthalidone (an isoindoline), quinethazone (a quinazoline), and ethacrnic acid were included in this investigation as examples of diuretics of other chemical types.

The effect of altered carbohydrate metabolism in pertussis-sensitized mice on anaphylaxis

Abstract An attenuated reponse to epinephrine-induced hyperglycemia has been demonstrated in rats injected with Bordetella pertussis alone and in mice sensitized with horse serum or in combination with B. pertussis . This response is not a reflection of reduced liver glycogen. In the mice sensitized with horse serum only, protection against anaphylaxis is afforded by some but not all hyperglycemia-inducing agents tested. Alloxan and epinephrine protect, whereas diazoxide does not. Alloxan was considerably less protective in the horse serum-pertussis-sensitized mouse. Diazoxide, glucose, and epinephrine did not protect. Prednisolone and betamethasone, at doses that protect against lethal anaphylaxis in the horse serum-pertussis-sensitized mouse, also restore epinephrine hyperglycemia in the pertussis rat. Possible mechanisms of protection of these compounds are discussed. No definite link between the carbohydrate abnormality of the pertussis animal and anaphylactic sensitivity has been established.

Effect of epinephrine on hepatic glycogen phosphorylase and synthetase activities in normal and pertussis-sensitized rats.

Abstract To investigate the nature of the diminished hyperglycemic response to epinephrine in pertussis-sensitized rats, we compared the response to epinephrine of the hepatic enzymes, glycogen phosphorylase and glycogen synthetase, and of peripheral lactate release in normal and sensitized rats. The epinephrine-induced activation of hepatic phosphorylase was markedly diminished in pertussis rats. Pertussis sensitization did not alter either the decrease in hepatic glycogen synthetase activity or the elevation of plasma lactate produced by epinephrine administration. The findings indicate that a diminished activation of hepatic phosphorylase, associated with and possibly dependent upon a relative hyperinsulinism, can account for the attenuated hyperglycemic response to epinephrine in pertussis rats.

Norepinephrine biosynthesis in the rat pancreas

Abstract The biosynthesis in vivo of norepinephrine was studied in rat pancreas with 14C-dopamine as precursor. It was shown that after i.m. injection 14C-dopamine was taken up by the pancreatic tissue, where this catecholamine was metabolized. Norepinephrine was the major transformation product found in the pancreas. Dopamine was metabolized faster in the pancreas than in the heart and the spleen. On the other hand, the concentration of the radioactivity at 30-min and 120-min time intervals was higher in the heart and spleen than in the pancreas.