EMD 68843, a serotonin reuptake inhibitor with selective presynaptic 5-HT1A receptor agonistic properties

The 5-HT1A receptor agonist 8-hydroxy-(di-n-propylamino)tetralin (8-OH-DPAT; 0.55 mg/kg s.c.) and the 5-HT (5-hydroxytryptamine, serotonin) reuptake inhibitor/5-HT1A receptor ligand 5-[4-[4-(5-cyano-3-indolyl)-butyl]-1-piperazinyl]-benzofuran-2-carbox ami de (EMD 68843; 55 mg/kg p.o.) inhibited ultrasonic vocalization in rats, an effect which was antagonized by the 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]-N-(2-pyridyl)- cyclohexancarboxamide (WAY 100635; 1.0 mg/kg s.c.). 8-OH-DPAT decreased body temperature in rats, an effect which was also antagonized by WAY 100635, whereas EMD 68843 neither affected body temperature by itself nor interacted with 8-OH-DPAT or WAY 100635. The selective 5-HT reuptake inhibitor fluoxetine (100 mg/kg p.o.) had no effect on ultrasonic vocalization or body temperature. Therefore EMD 68843 is suggested to be a 5-HT1A receptor agonist selective for presynaptic 5-HT1A receptors.