Samidorphan in Combination With Buprenorphine Improves Behavioral Deficits in Rats

Author(s):

In a poster presentation at the 73rd Annual Scientific Convention of the Society of Biological Psychiatry meeting in New York, New York, May 10 to 12, researchers reported about an adjunctive investigational drug therapy for major depressive disorder, alone and together with a selective serotonin reuptake inhibitor (SSRI), in rats resistant to SSRIs.

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In a poster presentation at the 73rd Annual Scientific Convention of the Society of Biological Psychiatry meeting in New York, New York, May 10 to 12, researchers reported about an adjunctive investigational drug therapy for major depressive disorder (MDD), alone and together with a selective serotonin reuptake inhibitor (SSRI), in rats resistant to SSRIs.

ALKS 5461, a combination of buprenorphine (BUP) and samidorphan (SAM), is an opioid system modulator under development for patients with MDD with inadequate response to conventional antidepressants.

The Wistar Kyoto (WKY) rat strain is a model that mimics some aspects of depression and anxiety and is reportedly insensitive to SSRI treatment.

To assess SSRI insensitivity, 8 rats received acute or repeated fluoxetine or escitalopram (ESC) treatment before exposure to the forced swim test (FST).

Both treatment-naïve and ESC-treated rats received a single subcutaneous injection of BUP:SAM before the FST.

Separate cohorts of rats (n = 8 per group) were dosed acutely with diazepam (DZ), ESC, or BUP:SAM 24 hours and were tested in the marble burying task to assess anxiolytic-like activity.

In the FST, neither acute nor chronic SSRI treatment altered immobility compared with vehicle controls.

Acute BUP:SAM significantly reduced immobility in both naive (P <.05) and ESC-treated rats (P <.01). BUP:SAM significantly reduced marble burying behavior 24 hours post injection (P <.01), whereas DZ and ESC were inactive under these treatment conditions.

The researchers said the data indicated that WKY rats are SSRI-insensitive when tested in the FST, and they may be a useful model for investigating novel antidepressants. The data also showed that the ALKS 4561 improves behavioral deficits in nonclinical tests of depression and anxiety.

Reference

Smith K, Eyerman DJ, Dean RL, Sanchez C. Samidorphan in combination with buprenorphine improves behavioral deficits in non-clinical tests of depression and anxiety using SSRI insensitive rats. Presented at: The 73rd Annual Scientific Convention of the Society of Biological Psychiatry Meeting; May 12, 2018; New York, New York. Abstract #S171.