The local anesthetic lidocaine was found to bind with high affinity (Kd=355 nM) to peripheral-type benzodiazepine receptors (PBR) in rat olfactory bulb homogenates. This high affinity, dose-related binding activity at the PBR was not shared by other local anesthetics cocaine, procaine or tetracaine, or by the anticonvulsant sodium valproate. However, the anticonvulsant carbamazepine did displace binding at the PBR in a dose-related manner. These results suggest that the anticonvulsant and/or antiarrhythmic effects of lidocaine and carbamazepine may involve a PBR component. These possibilities are currently being investigated. The regulation of central adenosine and beta-adrenergic receptors by alterations in thyroid function in rats is also being investigated. Preliminary results indicate that hyperthyroidism may down-regulate the number of striatal adenosine A2 binding sites with no alteration of beta-adrenergic receptors. Preliminary results also indicate that hypothyroidism may decrease cerebral cortical beta-adrenergic receptors. Studies on identifying the hypothesized central adenosine A3 receptor were started. A small component of apparently A1 binding is displaced by nicotinamide adenine dinucleotide (NAD) which was previously shown by others not to bind at adenosine receptors. [3H]NAD binding was shown to be stereospecific by autoradiographic analysis. [3H]NAD binding is partially inhibited by adenosine agonists and by carbamazepine. These preliminary results hint at the possibility of an unidentified adenosine receptor that also recognizes NAD. These investigations are only in the initial stages.
