Roxindole (EMD 49980) is a selective dopamine autoreceptor and 5-HT1A dual agonist and inhibitor of 5-hydroxytryptamine (5-HT) uptake with antipsychotic and antidepressant activity.Roxindole can be used to study Parkinson's and neurodivergence.

Roxindole has high affinity for hD3 as well as hD2 (short isomer) and hD4 (4-repeat isomer) receptors (pKi values of 8.93, 8.55 and 8.23, respectively). In addition, it had a high affinity for the hS-HT1A receptor (pKi = 9.42), but a low affinity for the 5-HT1B and 5-HT1D receptors (pKi values of 6.00 and 7.05, respectively). [1]

Roxindole（EMD 49980） inhibited apomorphine-induced climbing behavior in mice and stereotyped behavior in rats with ED50 of 1.4 mg/kg s.c. and 0.65 mg/kg s.c., respectively, and also inhibited conditioned avoidance responses in rats (ED50 = 1. 5 mg/kg s.c) [2];In the paradigm of co-treatment with haloperidol (1 mg/kg per day, orally), Roxindole（EMD 49980） (10 mg/kg per day, orally) did not alter the behavioral hypersensitivity measured after the drug washout phase as compared with the effect of haloperidol alone; if administration of Roxindole（EMD 49980） (10 mg/kg, i.v.) after the drug washout phase induced only weak stereotyped behaviors in haloperidol-hypersensitized rats, Roxindole（EMD 49980） did not induce either desensitization of the presynaptic or supersensitivity of the postsynaptic dopamine D2 receptor[3]; Roxindole (EMD 49980) (1, 3, 10 mg/kg; s.c) inhibits both effects of 8-OH-DPAT (flattened body and forepaw stamping) in normal rats (male Wistar 200-350g) [5].