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Local counter current transfer of substances between venous and arterial vessels has been found in the perihypophyseal vascular complex after administration into the supraorbital vein. The present experiments investigate whether similar transfer could be found after nasal administration of testosterone. Experiments were conducted on the model of isolated pig's head perfused with autologous blood through one carotid artery. Tritium labelled testosterone was infused onto the nasal mucous. Radioactivity was measured in blood samples collected from the contralateral carotid artery (indicator of transfer), in the venous effluent from the jugular veins (indicator of absorption), and in tissue samples from the olfactory bulb, olfactory triangle, hypothalamus, mammillary body, cortex, pons, cerebellum, neurohypophysis, adenohypophysis, pia vessels and perihypophyseal vascular complex. The absorption was 11.4 ±4.6 per cent (mean ± SEM) and 0.4 ±0.3 per cent of the instilled testosterone was transferred during the 25 min collection period. The uptake of radioactivity was seen in many of the brain tissue samples representing the brain, pituitary, pia vessels and cavernous sinus - carotid rete complex, although a clear pattern was not seen. Nasally administered drugs may thus reach the brain in a relatively higher concentration than it reaches the rest of the body. This makes targeted treatment of the brain a distinct possibility. Additionally, the treatment will decrease the first-passage metabolism in the liver.
The effect of chlorpromazine (CPZ) on the neurosecretory action of the hypothalamo-hypophyseal system was investigated in 72 male rats. The experimental animals received CPZ in a dose of 0.4 mg, 4.0 mg and 20.0 mg/kg b.w. for 30 days. The rats were sacrificed by decapitation at 24 h and 7 days after the last dose of the drug. The neurosecretory material was stained with paraldehyde fuchsin in the supraoptic nucleus, paraventricular nucleus, eminentia mediana and neurohypophysis, the tigroid was stained with toluidine blue and the acid phosphatase activity was evaluated histoenzymatically. It was found that CPZ reduced the content of the neurosecretory material after 24 h, while an increase was observed 7 days after the last drug administration.
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