Effects of opiranserin (Unafra) on mechanical nociceptive thresholds in Beagle dogs: a randomized crossover study.

OBJECTIVE

To evaluate the antinociceptive efficacy and safety of the novel analgesic opiranserin (a dual glycine transporter-2 inhibitor and 5-hydroxytryptamine 2A antagonist) in dogs using mechanical nociceptive threshold (MNT) testing, with low-dose remifentanil (positive control) and normal saline (negative control).

STUDY

DESIGN

Randomized, blinded, crossover study.

ANIMALS: Six healthy male Beagle dogs [aged 3.4-5.3 years, 13.1 ± 0.5 kg (mean ± standard deviation)].

METHODS

Each dog was given a 4-hour intravenous constant rate infusion (CRI) of opiranserin (5 mg kg-1 hour-1), remifentanil (4 μg kg-1 hour-1), or normal saline with ≥ 7 days inter-treatment interval. MNT (left metacarpal, carpal and metatarsal pad), pulse rate, and sedation scores were recorded at 0 (baseline), 30, 60, 120, 180, and 240 minutes. MNT and pulse rate were analyzed using linear mixed-effects models. Sedation scores were analyzed using Friedman's test.

RESULTS

With opiranserin, MNT increased from 30-240 minutes versus baseline (p < 0.001), and the opiranserin-saline difference increased over time (p < 0.001). With remifentanil, MNT increased versus baseline from 30 minutes (p < 0.001) without additional time-dependent increase. In a secondary comparison, MNT was higher with opiranserin than remifentanil from 60-240 minutes (all p values ≤ 0.036). Pulse rate decreased with remifentanil (p < 0.001), but not opiranserin or saline. Sedation was 0/12 with opiranserin and saline, and increased minimally with remifentanil (1/12). Vomiting (2/6 dogs) and nausea-like signs (5/6 dogs) were the main adverse events with opiranserin. All adverse effects resolved within 30 minutes of stopping the CRI. No psychomimetic or neurological signs were observed.

CONCLUSIONS AND CLINICAL RELEVANCE: A 4-hour CRI of opiranserin (5 mg kg-1 hour-1) increased MNTs during infusion in dogs without clinically relevant sedation or cardiovascular depression. These findings are consistent with antinociceptive activity under this experimental model.