5-Iodo-2-aminoindan, a nonneurotoxic analogue of p-iodoamphetamine

Journal Article · Tue Jan 01 00:00:00 EST 1991 · Pharmacology, Biochemistry and Behavior; (USA)

DOI:https://doi.org/10.1016/0091-3057(91)90601-W· OSTI ID:5583621

Nichols, D E; Johnson, M P; Oberlender, R ^[1]

---

1. Purdue Univ., West Lafayette, IN (USA)

A rigid analogue, 5-iodo-2-aminoindan (5-IAI), of the serotonin neurotoxic halogenated amphetamine p-iodoamphetamine (PIA) was pharmacologically evaluated for production of serotonin neurotoxicity. A comparison was also made between 5-IAI and PIA in the two-lever drug discrimination paradigm in rats trained to discriminate saline from 3,4-methylenedioxymethamphetamine (MDMA) or saline from the alpha-ethyl homologue of MDMA, MBDB. PIA and 5-IAI were both behaviorally active, and fully substituted in both groups of animals, but were considerably less potent than p-chloroamphetamine (PCA). PIA had about twice the potency of PCA as an inhibitor of {sup 3}H-5-HT uptake in rat brain cortical synaptosomes, while 5-IAI was only about 75% as potent as PCA in this assay. A single 40 mg/kg dose of PIA resulted in a 40% reduction of 5-HT and 5-HIAA levels and in the number of 5-HT uptake sites in rat cortex at one week sacrifice. The same dose of 5-IAI with one week sacrifice led to about a 15% decrease in 5-HIAA levels and number of 5-HT uptake sites, but only the latter was statistically significant. In rat hippocampus, PIA gave significant decreases in all serotonin markers examined, while 5-IAI slightly but significantly decreased only 5-HT levels. Neither compound produced any change in catecholamine or catecholamine metabolite levels. The results confirm earlier reports of the selective serotonin neurotoxicity of PIA, which is less severe than that of PCA, and also demonstrate that its rigid analogue 5-IAI does not appear to cause significant serotonin deficits in the rat.

• OSTI ID: 5583621
• Journal Information: Pharmacology, Biochemistry and Behavior; (USA), Vol. 38:1; ISSN 0091-3057
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
AMPHETAMINES
PHARMACOLOGY
SEROTONIN
UPTAKE
AUTORADIOGRAPHY
BRAIN
DOSE-RESPONSE RELATIONSHIPS
INHIBITION
NERVE CELLS
PIPERIDINES
RATS
TRITIUM COMPOUNDS
AMINES
ANALEPTICS
ANIMAL CELLS
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZINES
AZOLES
BODY
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
DRUGS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
INDOLES
MAMMALS
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PYRIDINES
PYRROLES
RADIOPROTECTIVE SUBSTANCES
RODENTS
SOMATIC CELLS
SYMPATHOMIMETICS
TRYPTAMINES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques