Abstract
In previous study, a series of benzamides was identified as potent antipsychotic agents. As a continuation of the program to discover novel antipsychotics, herein we reported the evaluation of a series of pyridinecarboxamide derivatives. The most promising compound 7h not only held good activities on dopamine D2, serotonin 5-HT1A and 5-HT2A receptors, but also exhibited low potency for α1A, H1 and 5-HT2C receptors, indicating a low propensity of side effects like orthostatic hypotension and weight gain. Furthermore, 7h exhibited more potent antipsychotic-like effect than aripiprazole in behavioral studies. The preliminary results were promising enough for further research around this scaffold.
Keywords:
5-HT(1A) receptor; Antipsychotic; Multi-receptor; PCP-induced hyperlocomotion; Pyridinecarboxamide.
Copyright © 2018 Elsevier Ltd. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antipsychotic Agents / chemical synthesis
-
Antipsychotic Agents / chemistry
-
Antipsychotic Agents / metabolism
-
Antipsychotic Agents / pharmacology*
-
Aripiprazole / pharmacology
-
Dopamine D2 Receptor Antagonists / chemical synthesis
-
Dopamine D2 Receptor Antagonists / chemistry
-
Dopamine D2 Receptor Antagonists / metabolism
-
Dopamine D2 Receptor Antagonists / pharmacology
-
Humans
-
Male
-
Mice, Inbred ICR
-
Microsomes, Liver / metabolism
-
Molecular Structure
-
Picolinic Acids / chemical synthesis
-
Picolinic Acids / chemistry
-
Picolinic Acids / metabolism
-
Picolinic Acids / pharmacology*
-
Risperidone / pharmacology
-
Serotonin 5-HT1 Receptor Antagonists / chemical synthesis
-
Serotonin 5-HT1 Receptor Antagonists / chemistry
-
Serotonin 5-HT1 Receptor Antagonists / metabolism
-
Serotonin 5-HT1 Receptor Antagonists / pharmacology
-
Serotonin 5-HT2 Receptor Antagonists / chemical synthesis
-
Serotonin 5-HT2 Receptor Antagonists / chemistry
-
Serotonin 5-HT2 Receptor Antagonists / metabolism
-
Serotonin 5-HT2 Receptor Antagonists / pharmacology
-
Structure-Activity Relationship
Substances
-
Antipsychotic Agents
-
Dopamine D2 Receptor Antagonists
-
Picolinic Acids
-
Serotonin 5-HT1 Receptor Antagonists
-
Serotonin 5-HT2 Receptor Antagonists
-
Aripiprazole
-
Risperidone