Involvement of the serotonergic system in the mode of action of the new potential antidepressant agent 5-methoxyindolyl-2-methylamine.
5-Methoxyindolyl-2-methylamine (PIM-35) is an indole derivative with effects in animals indicative of antidepressant properties. In the present study an attempt was made to gain some insight into the mechanism of its pharmacological activity. PIM-35 was compared with some antidepressants in tests for serotonin (5HT), noradrenaline (NA) and dopamine (DA) uptake inhibition in vitro. PIM-35 is a weak inhibitor of noradrenaline uptake as compared with the standards used. The IC50 value for dopamine uptake was similar to the value for imipramine and higher than that for amitriptyline, both these standards being considered as inhibitors of dopamine uptake. The influence of PIM-35 on serotonin uptake has been studied in a very preliminary experiment after single dose administration to rats. In a similar way paroxetine and chlorimipramine were studied. The inhibition produced by PIM-35 is similar to that produced by the standards. Radioligand binding techniques in rat brain ex vivo showed that chronic administration of PIM-35 produced no variation in the number or the affinity of alpha 2, beta 1- and beta 2-adrenoceptors. PIM-35 inhibits by 40% the number of 5HT2 receptors and does not modify the affinity for the ligand. PIM-35 has activity on the serotonergic system and in this way is similar to the antidepressants paroxetine and chlorimipramine.
Carranza Gómez-Carpintero
M C
MC
Department of Research, Laboratory Morrith, Madrid, Spain.
Ochoa Estomba
M C
MC
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D015306:Biogenic Monoamines / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008744:Methylamines / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D007211:Indoles; D008744:Methylamines; D009419:Nerve Tissue Proteins; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011985:Receptors, Serotonin; C083506:5-methoxyindolyl-2-methylamine; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine