Correlation between the distribution of 3H-labelled enkephalin in rat brain and the anatomical regions involved in enkephalin-induced seizures.

The correlation between the distribution of the intraventricularly (i.v.t.) administered delta agonist [3H](D-ala2,D-leu5)-enkephalin ([3H]DADL) and the anatomical regions involved in enkephalin-induced seizures has been studied in rat by using an autoradiographic method and recording of the electromyogram (EMG) and the electroencephalogram (EEG). The results indicate that within 10 min, the radioactivity of the intraventricularly administered drug reached all parts of the ventricular system, including the central canal of the spinal cord. However, within 2.5 min after the intraventricular administration of [3H]DADL, which corresponds to the onset of DADL-induced seizures, the substance appeared mainly in the left lateral ventricle and occasionally in the third ventricle. During the first 2.5 min the substance penetrated regularly into the surrounding periventricular tissue of the striatum, septum and hippocampus to a depth of about 100 microns. The most intensive and long-lasting epileptic discharges, exceeding 30 min were observed in the hippocampus, in contrast to the mild and short-lasting electrophysiological responses of the septum and corpus striatum. The experiments suggest that the short onset of enkephalin-induced excitatory phenomena is due to the rapid distribution and penetration of the substance in the surrounding periventricular tissue. According to these data, it is proposed that activation of delta opiate receptors, localized within the first 100 microns of the periventricular tissue, mainly in the hippocampus, is essential for the triggering of endorphin-induced seizure activity.

Excretion and distribution studies in rats with two forms of 14carbon-labelled polyvinylpyrrolidone with a relatively low mean molecular weight after intravenous administration.

Excretion and autoradiographic distribution studies were performed in rats with two 14C-labelled polyvinylpyrrolidone preparations, both of relatively low mean molecular weight but different in molecular weight distribution. At different time intervals after i.v. administration, elimination of radioactivity was found to be more complete for the preparation with the smallest fraction of molecules having a weight of over 25000, which is approximately the weight limit for rapid glomerular filtration in the rat. Our study demonstrates that the retention of PVP in organs, which in the literature are mentioned as target organs for PVP-toxicity, can be largely prevented by decreasing the fraction of molecules with a weight of more than 25000.

A combined study on the distribution of oxytetracycline and polyvinylpyrrolidone in rats.

With the purpose of studying the influence of polyvinylpyrrolidone (PVP) on the disposition of oxytetracycline (OTC), OTC was administered i.v. to male rats in two formulations, one of which contained 14C-labelled PVP. From the rats, whole-body sections (30 mum) were taken which were subjected to three analytical procedures: autoradiography to determine the distribution of the PVP-14C, fluorography and bioautography to obtain information on the OTC-distribution. The experimental results suggest equilibrium complex formation between OTC and PVP, it being mainly the complex which is i.v. injected when both products are combined in an injection formulation. Such complex formation can explain the lower toxicity of OTC when injected in combination with PVP as well as the slower build-up of OTC-levels in some organs, compared with that after OTC administration without PVP. Beyond this kinetic effect of PVP on the fate of OTC no evidence was obtained for an influence of PVP on the OTC distribution pattern per se, or on its ultimate antibiotic activity in the different organs. Some details of the OTC and especially of the PVP distribution are discussed.