AMI-193

Spiramide (AMI-193) is a potent and selective antagonist of 5-HT2 and dopamine D2 receptor, with Kis of 2 nM and 3 nM, respectively. Spiramide has >2000-fold selectivity for 5-HT2 versus 5-HT1C (Ki=4300 nM) receptors. Spiramide exhibits antipsychotic activity[1][2][3].

Signaling Pathways >> GPCR/G Protein >> Dopamine Receptor

Signaling Pathways >> Neuronal Signaling >> Dopamine Receptor

Research Areas >> Neurological Disease

Signaling Pathways >> GPCR/G Protein >> 5-HT Receptor

Signaling Pathways >> Neuronal Signaling >> 5-HT Receptor

5-HT2 Receptor:2 nM (Ki)

D2 Receptor:3 nM (Ki)

5-HT1A Receptor:50 nM (Ki)

D1 Receptor:2530 nM (Ki)

5-HT1C Receptor:4300 nM (Ki)

Spiramide retains affinity for 5-HT1A sites (Ki=50 nM) and also binds at dopamine D2 sites (Ki=3 nM), but possesses low affinity for dopamine D1 sites (Ki=2530 nM)[1].

AMI-193 (0.003-0.01 mg/kg; i.m.) dose-dependently decreases response rate in monkeys under a fixed-interval (FI) schedule of stimulus termination[2]. AMI-193 (0.003-0.01 mg/kg; i.m.) attenuates the discriminative-stimulus effects of cocaine in drug-discrimination experiments[2]. AMI-193 (0.003-0.01 mg/kg; i.m.) reduces response rate under a second-order schedule of i.v. self-administration of cocaine (0.1 mg/infusion)[2]. Animal Model: Adult male squirrel monkeys (850-1300 g)[2] Dosage: 0.003, 0.01 mg/kg Administration: I.m. on Tuesday, Wednesday, and Thursday the following week Result: Decreased the response rate. The rate-decreasing effects were reversed by cocaine.

[1]. Ismaiel AM, et, al. Antagonism of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane stimulus with a newly identified 5-HT2- versus 5-HT1C-selective antagonist. J Med Chem. 1993 Aug 20;36(17):2519-25.

[2]. Czoty PW, et, al. Behavioral effects of AMI-193, a 5-HT(2A)- and dopamine D(2)-receptor antagonist, in the squirrel monkey. Pharmacol Biochem Behav. 2000 Oct;67(2):257-64.

[3]. Kjellberg B, et, al. Partial restoration by a neuroleptic (spiramide) of items of grooming behaviour suppressed by amphetamine. Arch Int Pharmacodyn Ther. 1974 Jul;210(1):61-6.