ABSTRACT
It has been possible to prepare from 8-(2-phenylethyl)-1,3,8-triaza [4, 5] spirodecane-2,4-dione a new series of derivatives substituted on the nitrogen atom in the 3-position of the hydantoïn ring. Several compounds exhibited sedative, anticonvulsant and anxiolytic activities. The aryl or heteroaryl-piperazinomethyl substituted compounds were the most active derivatives. "Buspirone-like" anxiolytic effects were found in some compounds from 5 mg/kg dose per os.
Subject(s)
Central Nervous System Agents/chemical synthesis , Animals , Anti-Anxiety Agents/chemical synthesis , Anti-Anxiety Agents/pharmacology , Anti-Anxiety Agents/toxicity , Anticonvulsants/chemical synthesis , Anticonvulsants/pharmacology , Anticonvulsants/toxicity , Central Nervous System Agents/pharmacology , Central Nervous System Agents/toxicity , Hypnotics and Sedatives/chemical synthesis , Hypnotics and Sedatives/pharmacology , Hypnotics and Sedatives/toxicity , Male , MiceABSTRACT
A series of 6,8-diaryl-1,2,4-triazolo[4,3-b] and 1,2,3,4-tetrazolo[1,5-b]pyridazines was synthesized from suitable chloropyridazines. The compounds were screened in mice for their ability to antagonize maximal electroshock-, pentylenetetrazole- and bicuculline-induced seizures; sedative effects were evaluated by a study of the spontaneous motor activity. Some of pyridazine derivatives exhibited appreciable anticonvulsant activity. Substituting the phenyl ring in the 6-position with an halogen atom led to a substantial increase of activity. Furthermore, none of the compounds was notably active in tests predictive of anxiolytic activity.
Subject(s)
Anti-Anxiety Agents/chemical synthesis , Anticonvulsants/chemical synthesis , Azoles/chemical synthesis , Pyridazines/chemical synthesis , Tetrazoles/chemical synthesis , Triazoles/chemical synthesis , Animals , Behavior, Animal/drug effects , Bicuculline , Chemical Phenomena , Chemistry , Electroshock , Hypnotics and Sedatives , Mice , Motor Activity/drug effects , Pentylenetetrazole , Pyridazines/pharmacology , Pyridazines/toxicity , Seizures/chemically induced , Seizures/prevention & control , Tetrazoles/pharmacology , Tetrazoles/toxicity , Triazoles/pharmacology , Triazoles/toxicityABSTRACT
The reaction of 3-chloro pyridazines with various amines led to a series of minaprine analogues. Most of them exhibited significant antidepressant activity. The influence of the substituents attached to the pyridazine ring was discussed.
Subject(s)
Antidepressive Agents/chemical synthesis , Pyridazines/chemical synthesis , Animals , Antidepressive Agents/toxicity , Catalepsy/chemically induced , Chemical Phenomena , Chemistry , Female , Male , Mice , Morpholines/antagonists & inhibitors , Pyridazines/pharmacology , Pyridazines/toxicity , Rats , Rats, Inbred Strains , Reserpine/antagonists & inhibitorsSubject(s)
Histamine H1 Antagonists/chemical synthesis , Nitrogen Oxides/chemical synthesis , Animals , Dose-Response Relationship, Drug , Guinea Pigs , Histamine H1 Antagonists/pharmacology , Ileum/drug effects , Male , Mice , Mice, Inbred Strains , Nitrogen Oxides/pharmacology , Passive Cutaneous Anaphylaxis , Rats , Rats, Inbred StrainsABSTRACT
A series of pyrazoline derivatives was synthetised and evaluated for toxicological and pharmacological effects; analgesic, hypnotic, anti-inflammatory, antipyretic and cardiovascular properties were screened. Tested compounds were found to have a low toxicity; one of them showed a good analgesic activity without side effects.
