Effect of Oral OPC-28326, a Selective Femoral Arterial Vasodilator, on Hindlimb Subcutaneous Tissue Temperature in Conscious Dogs Under Buprenorphine Sedation

Abstract

ABSTRACT-In dogs, rectal temperature was decreased to about 36°C at 2 to 2.5 h after sedation with buprenorphine (0.3 mg/body, i.m.), and hindlimb subcutaneous tissue temperature (T SC) in the thigh decreased in a similar manner. TSC in the dorsum of the foot showed a greater decrease than that in the thigh. OPC-28326 (4-(N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionyl-aminobenzoyl) piperidine hydrochloride monohydrate) at doses of 0.3, 1.0 and 3.0 mg/kg, p.o. inhibited the buprenorphine-induced decrease in TSC in the dorsum dose-dependently, but had little effect on that in the thigh or rectal temperature. In conclusion, TSC in the extremities were more sensitive to core temperature and peripheral circulation.Keywords: Peripheral circulation, Subcutaneous temperature, Conscious dog OPC-28326 (4-(N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionyl-aminobenzoyl) piperidine hydrochloride monohydrate) is a newly developed, selective vasodilator increasing the blood flow of the femoral artery (1). This drug has little effect on other cardiovascular parameters, such as blood pressure, heart rate, contractile force of myocardium, and blood flow in other areas, such as the carotid, vertebral, coronary, renal and mesentery arteries (1). a 2 -Adrenoceptor blocking action of OPC-28326 may be involved its selective vasodilator action on the femoral artery (2). To evaluate the effects of oral administration of OPC-28326, we measured subcutaneous temperature using a wire-type thermometer in conscious dogs sedated with buprenorphine. It has been reported that intravenously injected buprenorphine exerted hypothermic action on body temperature in a chronic spinal dog (3). We found that buprenorphine decreased subcoutaneous temperature in the periphery (the dorsum of the foot) more greatly than that in the thigh of dogs. In the present study, we examined the effects of OPC-28326 on subcutaneous temperature in the dogs sedated with buprenorphine, and we measured rectal temperature and subcutaneous temperature in the dorsum of the foot and thigh.Male beagle dogs weighing 9 -12 kg were housed during the experiment in a sound-proof room in which temperature and humidity were controlled at 23 ± 2°C and 60 ± 10%, respectively. A thermometer (Electronic thermometer; Seiwa ME Laboratory, Tokyo) was inserted into the rectum. After the animals were restrained in a standing position, buprenorphine at the dose of 0.3 mg / body was administered intramuscularly. Changes in rectal temperature were measured for 5 h at 30-min intervals. The changes in rectal temperature of buprenorphine-treated dogs were compared with those of non-treated dogs.Dogs were restrained in a standing position in slings, and buprenorphine was injected into the muscles of the left thigh. When the dogs were adequately sedated (approximately 30 min after buprenorphine), a needle-type probe (TN-800; Unique Medical, Tokyo) of a biothermometer (TME-300, Unique Medical) was placed in the subcutaneous tissues in the dorsum of the right foot and in the right thigh...

Pyrogens Enhance β-Endorphin Release in Hypothalamus and Trigger Fever That Can Be Attenuated by Buprenorphine

“…Activation of m -opioid receptor in brain has also been shown to mediate the fever response in rats (18 -21). Furthermore, a more recent report showed that the rectal temperature of dogs was decreased to about 36°C at 2 to 2.5 h after sedation with intra-muscular administration of buprenorphine (22). This raises the additional possibility that buprenorphine has an antipyretic action.…”

Efficacy and tolerability of a selective α2C‐adrenergic receptor blocker in recovery from cold‐induced vasospasm in scleroderma patients: A single‐center, double‐blind, placebo‐controlled, randomized crossover study

“…OPC‐28326 (4‐[N‐methyl‐2‐phenylethyl‐amino]‐1‐[3,5‐dimethyl‐4‐propionyl‐aminobenzoyl] piperidine hydrochloride monohydrate), a piperidine derivative, is a selective α‐adrenergic antagonist with preferential binding to the α 2C ‐AR subtype (α 2C is several‐fold stronger than α 2B , followed in decreasing strength by α 2A and α 1 ) (4–6). Animal studies involving OPC‐28326 have demonstrated improved hind‐limb blood flow during cold exposure and normalized skin temperature under anesthesia with this drug (6, 7). OPC‐28326 has been administered to patients with atherosclerotic peripheral vascular disease and is well tolerated in single doses up to 240 mg.…”

OPC-28326, a selective peripheral vasodilator with angiogenic activity, mitigates postinfarction cardiac remodeling

“…OPC-28326 acts as an ␣ 2 -adrenoceptor antagonist, showing the highest affinity for the ␣ 2C -adrenoceptor subtype (28,34). In addition, an earlier study reported that in an ischemic leg model OPC-28326 also exerted angiogenic effects via the Akt/endothelial nitric oxide synthase (eNOS) pathway (33).…”