Serotonergic regulation of cortisol secretion in dogs.

The role of serotonin (5-HT) in the control of serum cortisol secretion was studied in 50 conscious beagle dogs. A significant rise in corticosteroids was observed after 1.5 and 3 mg/kg (P less than 0.01) iv fenfluramine, an indirect serotonergic agonist, as well as after 2 (P less than 0.05) and 3 mg/kg (P less than 0.01) iv quipazine, a direct agonist of 5-HT receptors. Both drugs exhibited a dose-related effect. A lower dose of fenfluramine, 0.5 mg/kg, was ineffective when administered iv, but raised serum cortisol (P less than 0.05) after direct injection into a lateral cerebral ventricle, through a chronically implanted brain cannula. The marked increases in corticosteroid concentration produced by the highest fenfluramine and quipazine doses were completely abolished by pretreatment with ketanserin, an antagonist of 5-HT2 receptors, which did not affect cortisol secretion when administered alone. These data suggest that brain serotonergic system plays a role in the control of cortisol secretion in conscious dogs.

Synthesis and biological activity of new 2-nitroimidazole derivatives.

In an earlier paper we described the synthesis and the antitrichomonas activity of 2-nitro-alpha,alpha,1-trimethyl-1H-imidazole-5-methanol (2). Starting from this compound, several derivatives have been synthesized. Among these, the phenyl carbonate 8 has been shown to possess activity equal to that of 2 and to be less toxic. This compound therefore is interesting in comparison with some antitrichomonas agents currently in use clinically. Before undertaking an in-depth investigation, compound 8 was subjected to some studies to see whether it has any effects on the central nervous system (CNS). Preliminary results show that, at therapeutic doses, it might induce unwanted CNS effects to a lesser degree than metronidazole.

Zetidoline, a novel neuroleptic, activates nigral dopaminergic neurons in rats.

Zetidoline (ZET), a rather selective dopamine (DA) D2-receptor blocker, was found to be equipotent to haloperidol and over 300 times as potent as sulpiride in activating the firing rate of substantia nigra dopaminergic neurons (SN-DA neurons) in unanesthetized rats. Moreover, like classic and atypical neuroleptics, ZET reversed and prevented apomorphine-induced inhibition of SN-DA neurons.

[Bicyclic piperazine homologues XIV (1). Synthesis and analgesic activity of 3,8-diaza-bicyclo[3.2.1.] octane derivatives]. / Omolochi biciclici della piperazina. Nota XIV (1) Sintesi ed attività analgesica di derivati del 3,8-diazabiciclo [3.2.1] ottano.

The synthesis of two new series of 3,8-diazabicyclo [3.2.1] octane derivatives is described. The first series includes some 3-(or 8)-allyl and 3-(or 8)-(3,3-dimethylallyl) derivatives of 3,8-diazabicyclo [3.2.1] octane and 3,8-diazabicyclo [3.2.1] octane-2-one. The second series includes some esters and carbamates of 3-(3-hydroxy-3-methyl)butyl-3,8-diazabicyclo [3.2.1] octane. Two new 3,8-diazabicyclo [3.2.1] octane derivatives structurally related to propoxyphene are also described. Some pharmacological data of these compounds are reported.

[Synthesis and pharmacologic activity of derivatives of 3-aminopropiophenone and 3-aminomethylcamphor]. / Sintesi ed attività farmacologica di derivati di 3-aminopropiofenoni e di 3-aminometilcanfore.

As a part of a research on analgesic compounds 0-(4-methoxyphenyl)carbamoyl-3-aminopropiophenone oximes, 0-(4-methoxyphenyl)-carbamoyl-3-aminomethylcamphor oximes and 4-(4-methoxyphenyl)semicarbazones of 3-aminopropiophenones were prepared. The analgesic activity of these compounds was tested and the results of pharmacological screening are discussed.

[Derivatives of 2,3,5,6,7,7a-hexahydro-1,3-dioxo-1H-pyrrolo[1,2-c]imidazol -5-carboxylic acids]. / Derivati degli acidi 2,3,5,6,7,7a-esaidro-1,3-dioxo-1H-pirrolo[1,2-]i midazolo-5-carbossilici.

The synthesis of the above-mentioned compounds, starting from the diethyl ester of 2,5-pyrrolidine dicarboxylic acid, is reported. The cis and trans isomers od the 2-phenylsubstituted acid were separated, and the trans form was resolved into the two chiral forms. Some amides were also prepared from these acids. The thio analogs (XIII) and (XVI) and the partially reduced derivatives (XIV) were synthesized. Some amides (VI) showed an interesting anti-anxiety effect in pharmacological models.

Synthesis of new psychotropic 2-imidazolidinones.

The report describes the synthesis and pharmacology of some new derivatives of 1-(m or p-chlorophenyl)-2-imidazolidinone. These compounds were obtained either by reacting an amine with an N-(2-chloroethyl)-2-imidazolidinone or by reacting a 2-chloroethylamine with an N-substituted-2-imidazolidinone. Two compounds (II f, h) showed interesting psychotropic activity.

Synthesis and preliminary pharmacological studies of some 3-substituted 5-amino-1,2,4-oxadiazoles.

Treatment of 4(5)-alkyl (or aryl)-2-aminoimidazoles with isoamyl nitrite in acetic acid gave rise to the corresponding 5(4)-substituted 2-amino-4(5)-hydroxyimino-4(5)H-imidazoles which were transformed into 3-acyl (or aroyl)-5-amino-1,2,4-oxadiazoles when treated in aqueous suspension. The results of a preliminary pharmacological investigation showed an interesting depressant activity on the CNS for one of these compounds, 5-amino-3-benzoyl-1,2,4-oxadiazole (III c). The pharmacological activities are correlated with the chemical substitutions on the oxadiazole ring.

Highly selective antiinflammatory and analgesic activity of 3-(1-methylethyl)-2-(4-methoxyphenyl)-3H-naphth[1,2-d]imidazole, a new non-acidic molecule.

3-(1-Methylethyl)-2-(4-methoxyphenyl)-3H-naphth[1,2-d] imidazole (MDL-035) has antiinflammatory activity in various antiinflammatory models such as carrageenin and nystatin oedemas, cotton pellet granuloma and adjuvant arthritis. The antiinflammatory potency of MDL-035 is greater than that of acetylsalicylic acid and phenylbutazone, but lower than that of indomethacin. MDL-035 has practically no gastroulcerogenic activity in rats, does not affect water or salt excretion, has no hormonal or antihormonal effects and has no other unwanted pharmacological effects. Its acute toxicity is very low.