Monograph: |
AGOMELATINE
AGOMELATINE IS STRUCTURALLY CLOSELY RELATED TO MELATONIN. AGOMELATINE IS A POTENT AGONIST AT MELATONIN RECEPTORS AND AN ANTAGONIST AT SEROTONIN-2C (5-HT2C) RECEPTORS, TESTED IN AN ANIMAL MODEL OF DEPRESSION. AGOMELATINE WAS DEVELOPED IN EUROPE BY SERVIER LABORATORIES LTD. AND SUBMITTED TO THE EUROPEAN MEDICINES AGENCY (EMA) IN 2005. THE COMMITTEE FOR MEDICAL PRODUCTS FOR HUMAN USE (CHMP) RECOMMENDED REFUSAL OF MARKETING AUTHORIZATION ON 27 JULY 2006. THE MAJOR CONCERN WAS THAT EFFICACY HAD NOT BEEN SUFFICIENTLY SHOWN. IN 2006 SERVIER SOLD THE RIGHTS TO DEVELOP AGOMELATINE IN THE US TO NOVARTIS.
THE DEVELOPMENT FOR THE US MARKET WAS DISCONTINUED IN OCTOBER 2011. IT IS CURRENTLY SOLD IN AUSTRALIA UNDER THE VALDOXAN TRADE NAME.
INDICATION
AGOMELATINE IS INDICATED TO TREAT MAJOR DEPRESSIVE EPISODES IN ADULTS.
PHARMACODYNAMICS
AGOMELATINE RESYNCHRONISES CIRCADIAN RHYTHMS IN ANIMAL MODELS OF DELAYED SLEEP PHASE SYNDROME AND OTHER CIRCADIAN RHYTHM DISRUPTIONS. IT INCREASES NORADRENALINE AND DOPAMINE RELEASE SPECIFICALLY IN THE FRONTAL CORTEX AND HAS NO INFLUENCE ON THE EXTRACELLULAR LEVELS OF SEROTONIN. AGOMELATINE HAS SHOWN AN ANTIDEPRESSANT-LIKE EFFECT IN ANIMAL DEPRESSION MODELS, (LEARNED HELPLESSNESS TEST, DESPAIR TEST, AND CHRONIC MILD STRESS) CIRCADIAN RHYTHM DESYNCHRONISATION, AND IN STRESS AND ANXIETY MODELS. IN HUMANS, AGOMELATINE HAS POSITIVE PHASE SHIFTING PROPERTIES; IT INDUCES A PHASE ADVANCE OF SLEEP, BODY TEMPERATURE DECLINE AND MELATONIN ONSET. CONTROLLED STUDIES IN HUMANS HAVE SHOWN THAT AGOMELATINE IS AS EFFECTIVE AS THE SSRI ANTIDEPRESSANTS PAROXETINE AND SERTRALINE IN THE TREATMENT OF MAJOR DEPRESSION
MECHANISM OF ACTION
THE NOVEL ANTIDEPRESSANT AGENT, AGOMELATINE, BEHAVES AS AN AGONIST AT MELATONIN RECEPTORS (MT1 AND MT2) AND AS AN ANTAGONIST AT SEROTONIN (5-HT)(2C) RECEPTORS.
DRUG INTERACTION
(R)-WARFARIN THE METABOLISM OF (R)-WARFARIN CAN BE DECREASED WHEN COMBINED WITH AGOMELATINE.
(S)-WARFARIN THE METABOLISM OF (S)-WARFARIN CAN BE DECREASED WHEN COMBINED WITH AGOMELATINE.
2,5-DIMETHOXY-4-ETHYLTHIOAMPHETAMINE THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN AGOMELATINE IS COMBINED WITH 2,5-DIMETHOXY-4-ETHYLTHIOAMPHETAMINE.
4-BROMO-2,5-DIMETHOXYAMPHETAMINE THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN 4-BROMO-2,5-DIMETHOXYAMPHETAMINE IS COMBINED WITH AGOMELATINE.
4-HYDROXYCOUMARIN THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN AGOMELATINE IS COMBINED WITH 4-HYDROXYCOUMARIN.
4-METHOXYAMPHETAMINE THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN 4-METHOXYAMPHETAMINE IS COMBINED WITH AGOMELATINE.
5-METHOXY-N,N-DIMETHYLTRYPTAMINE THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN AGOMELATINE IS COMBINED WITH 5-METHOXY-N,N-DIMETHYLTRYPTAMINE.
6-O-BENZYLGUANINE THE METABOLISM OF 6-O-BENZYLGUANINE CAN BE DECREASED WHEN COMBINED WITH AGOMELATINE.
7-NITROINDAZOLE THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN 7-NITROINDAZOLE IS COMBINED WITH AGOMELATINE.
7,8-DICHLORO-1,2,3,4-TETRAHYDROISOQUINOLINE THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN AGOMELATINE IS COMBINED WITH 7,8-DICHLORO-1,2,3,4-TETRAHYDROISOQUINOLINE.
8-AZAGUANINE THE METABOLISM OF AGOMELATINE CAN BE DECREASED WHEN COMBINED WITH 8-AZAGUANINE.
8-CHLOROTHEOPHYLLINE THE METABOLISM OF 8-CHLOROTHEOPHYLLINE CAN BE DECREASED WHEN COMBINED WITH AGOMELATINE.
9-DEAZAGUANINE THE METABOLISM OF AGOMELATINE CAN BE DECREASED WHEN COMBINED WITH 9-DEAZAGUANINE.
9-METHYLGUANINE THE METABOLISM OF AGOMELATINE CAN BE DECREASED WHEN COMBINED WITH 9-METHYLGUANINE.
ABATACEPT THE METABOLISM OF AGOMELATINE CAN BE INCREASED WHEN COMBINED WITH ABATACEPT.
ABIRATERONE THE SERUM CONCENTRATION OF AGOMELATINE CAN BE INCREASED WHEN IT IS COMBINED WITH ABIRATERONE.
ACEFYLLINE THE METABOLISM OF ACEFYLLINE CAN BE DECREASED WHEN COMBINED WITH AGOMELATINE.
ACENOCOUMAROL THE METABOLISM OF ACENOCOUMAROL CAN BE DECREASED WHEN COMBINED WITH AGOMELATINE.
ACEPROMAZINE THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN ACEPROMAZINE IS COMBINED WITH AGOMELATINE.
ACEPROMETAZINE THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN ACEPROMETAZINE IS COMBINED WITH AGOMELATINE.
ACETAMINOPHEN THE METABOLISM OF AGOMELATINE CAN BE DECREASED WHEN COMBINED WITH ACETAMINOPHEN.
ACETAZOLAMIDE THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN ACETAZOLAMIDE IS COMBINED WITH AGOMELATINE.
ACETOHEXAMIDE THE METABOLISM OF ACETOHEXAMIDE CAN BE DECREASED WHEN COMBINED WITH AGOMELATINE.
ACETOPHENAZINE THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN ACETOPHENAZINE IS COMBINED WITH AGOMELATINE.
ACETYLGLYCINAMIDE CHLORAL HYDRATE THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN AGOMELATINE IS COMBINED WITH ACETYLGLYCINAMIDE CHLORAL HYDRATE.
ACETYLSALICYLIC ACID THE METABOLISM OF ACETYLSALICYLIC ACID CAN BE DECREASED WHEN COMBINED WITH AGOMELATINE.
ACLIDINIUM AGOMELATINE MAY INCREASE THE CENTRAL NERVOUS SYSTEM DEPRESSANT (CNS DEPRESSANT) ACTIVITIES OF ACLIDINIUM.
ACYCLOVIR THE METABOLISM OF AGOMELATINE CAN BE DECREASED WHEN COMBINED WITH ACYCLOVIR.
ADALIMUMAB THE METABOLISM OF AGOMELATINE CAN BE INCREASED WHEN COMBINED WITH ADALIMUMAB.
ADINAZOLAM THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN ADINAZOLAM IS COMBINED WITH AGOMELATINE.
ADIPIPLON THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN ADIPIPLON IS COMBINED WITH AGOMELATINE.
AFELIMOMAB THE METABOLISM OF AGOMELATINE CAN BE INCREASED WHEN COMBINED WITH AFELIMOMAB.
AJULEMIC ACID THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN AJULEMIC ACID IS COMBINED WITH AGOMELATINE.
ALAPROCLATE THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN AGOMELATINE IS COMBINED WITH ALAPROCLATE.
ALBENDAZOLE THE METABOLISM OF AGOMELATINE CAN BE DECREASED WHEN COMBINED WITH ALBENDAZOLE.
ALBINTERFERON ALFA-2B THE METABOLISM OF AGOMELATINE CAN BE DECREASED WHEN COMBINED WITH ALBINTERFERON ALFA-2B.
ALCURONIUM THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN AGOMELATINE IS COMBINED WITH ALCURONIUM.
ALFAXALONE THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN AGOMELATINE IS COMBINED WITH ALFAXALONE.
ALFENTANIL THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN ALFENTANIL IS COMBINED WITH AGOMELATINE.
ALIMEMAZINE THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN ALIMEMAZINE IS COMBINED WITH AGOMELATINE.
ALLOBARBITAL THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN AGOMELATINE IS COMBINED WITH ALLOBARBITAL.
ALMOTRIPTAN THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN ALMOTRIPTAN IS COMBINED WITH AGOMELATINE.
ALOSETRON THE SERUM CONCENTRATION OF AGOMELATINE CAN BE INCREASED WHEN IT IS COMBINED WITH ALOSETRON.
ALPHACETYLMETHADOL THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN ALPHACETYLMETHADOL IS COMBINED WITH AGOMELATINE.
ALPHAPRODINE THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN AGOMELATINE IS COMBINED WITH ALPHAPRODINE.
ALPRAZOLAM THE METABOLISM OF ALPRAZOLAM CAN BE DECREASED WHEN COMBINED WITH AGOMELATINE.
ALPRENOLOL THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN ALPRENOLOL IS COMBINED WITH AGOMELATINE.
ALVERINE THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN ALVERINE IS COMBINED WITH AGOMELATINE.
AMINEPTINE THE RISK OR SEVERITY OF ADVERSE EFFECTS CAN BE INCREASED WHEN AMINEPTINE IS COMBINED WITH AGOMELATINE.
AMINOPHENAZONE THE METABOLISM OF AGOMELATINE CAN BE DECREASED WHEN COMBINED WITH AMINOPHENAZONE.
|