The potent non-peptide B₂ receptor (R) antagonist, Anatibant mesylate (Ms) (LF 16-0687 Ms), reduces brain edema and improves neurological function recovery in various focal and diffuse models of traumatic brain injury in rodents. In the present study, alteration of kinin B₁ and B₂R after closed head trauma (CHT) and in vivo binding properties of Anatibant Ms (3 mg/kg, s.c.) injected 30 min after CHT were studied in mice by autoradiography using the radioligands [¹²⁵I]HPP-Hoe 140 (B₂R), and [¹²⁵I]HPP-des-Arg¹⁰-Hoe 140 (B₁R). Whereas B₁R is barely detected in most brain regions, B₂R is extensively distributed, displaying the highest densities in the hindbrain. CHT was associated with a slight increase of B₁R and a decrease of B₂R (10–50%) in several brain regions. Anatibant Ms (Ki= 22 pM) displaced the B₂R radioligand from its binding sites in several areas of the forebrain, basal ganglia and hindbrain. Displacement was achieved in 1 h and persisted at 4 h post-injection. The inhibition did not exceed 50% of the total specific binding in non-injured mice. After CHT, the displacement by Anatibant Ms was higher and almost complete in the cortex, caudate putamen, thalamus, hippocampus, medial geniculate nucleus, ventral tegmental area, and raphe. Evans blue extravasation in brain tissue at 4 h after CHT was abolished by Anatibant Ms. It appeared that Anatibant Ms penetrated into the brain in sufficient amounts, particularly after disruption of the blood–brain barrier, to account for its B₂R-mediated neuro- and vascular protective effects. The diminished binding of B₂R after CHT may reflect the occupancy or internalization of B₂R following the endogenous production of bradykinin (BK).

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Autoradiographic Analysis of Mouse Brain Kinin B 1 and B 2 Receptors after Closed Head Trauma and Ability of Anatibant Mesylate to Cross the Blood–Brain Barrier