Selectivity of action of typical and atypical antipsychotic drugs as antagonists of the behavioral effects of 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI)

doi:10.1016/S0278-5846(99)00014-7

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Volume 23, Issue 3, April 1999, Pages 533-544

https://doi.org/10.1016/S0278-5846(99)00014-7 Get rights and content

Abstract

1.
1. There has been considerable research in the field of schizophrenia over the past few years with emphasis on the discovery of better drugs, particularly those with 5-HT2 antagonist activity.
2.
2. In an effort to enhance identification of such compounds and to further understand the contribution of 5-HT2 activity to the effects of antipsychotic drugs, a series of conventional, atypical and purported antipsychotic compounds were assessed as antagonists of DOI-induced behaviors in rats.
3.
3. DOI (l-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride) is an hallucinogen having high aIEnity and selectivity as an agonist at 5-HT_2A/2C receptors. Over a 30-min period after injection, DOI (0.3 – 10.0 mg/kg; i.p.) produced dose-related behavioral effects including head-and-body shakes, forepaw tapping and skin-jerks. Effects of the antipsychotic drugs and other compounds (30 min pretreatment; i.p.) were examined against a fixed dose of DOI (3.0 mg/kg).
4.
4. In a dose-dependent manner, M100907 (MDL 100, 907), risperidone, haloperidol, clozapine, iloperidone, olanzapine, amperozide, remoxipride, ritanserin and the neurotensin agonist NT1 (N^αleArg-Lys-Pro-Trp-Tle-Leu) antagonized each of the three behavioral effects of DOI. Drugs attenuating the head-and-body shakes were equally effective in blocking both forepaw tapping and skin-jerks indicating that these behaviors are mediated by similar mechanisms. The following compounds had either inconsistent or no effect on the DOI-induced behaviors: SB 200646A, citalopram, imipramine, fluoxetine, morphine, CP 99994, diazepam, ondansetron and SKF 97541.
5.
5. The data show that antipsychotic agents, as a drug class, effectively block the effects of DOI. These actions are selective, as a series of nine non-antipsychotic and centrally-acting drugs were generally inactive in the procedure.

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Full length original paper experimental laboratory studySelectivity of action of typical and atypical antipsychotic drugs as antagonists of the behavioral effects of 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI)

Abstract

Schizophrenia Research

Gen. Pharmacol.

Life Sci.

Behav. Brain Res.

Brain Research.

Neuroscience

Neurosci. Lett.

Life Sci.

Eur. J. Pharmacol.

Peptides

Eur. J. Pharmacol.

Agonist properties of a stable hexapeptide analog of neurotensin, NαMethyl-Arg-Lys-Pro-Trp-Tle-Leu (NT1)

Biochem. Pharmacol.

The neurokininl receptor antagonist CP- 99, 994 reduces catalepsy produced by the dopamine D2 receptor antagonist raclopridexorrelation with extracellular acetylcholine levels in striatum

J. Pharmacol. Exp. Ther.

The neurobiology of neurotensin

Full length original paper experimental laboratory study
Selectivity of action of typical and atypical antipsychotic drugs as antagonists of the behavioral effects of 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI)

Agonist properties of a stable hexapeptide analog of neurotensin, N^αMethyl-Arg-Lys-Pro-Trp-Tle-Leu (NT1)