Effect of phenylethanolamine N-methyltransferase inhibitor, CGS19281A, on the alpha-2-adrenoceptor function in the hypothalamus of rats in comparison with SKF29661, SKF64139 and yohimbine.

CGS19281A, a phenylethanolamine N-methyltransferase (PNMT) inhibitor, is reported not to inhibit alpha-2-adrenoceptor activity, in vitro. Effects of CGS19281A on the hypothalamic alpha-2-adrenoceptor function were studied in vivo in male Wistar rats. Agents used as controls were SKF29661, which is a selective peripheral PNMT inhibitor, SKF64139, a PNMT inhibitor that inhibits equally both alpha-2-adrenoceptor activity and PNMT, and yohimbine, an alpha-2-adrenoceptor inhibitor that does not inhibit PNMT. Following the administration of PNMT inhibitors, hypothalamic 3-methoxy 4-hydroxy phenylglycol (MHPG) was measured during micro brain dialysis to observe its fluctuations. Effects of PNMT inhibitors on growth hormone (GH) secretion caused by clonidine were examined in order to assess the effects of PNMT inhibitors on postsynaptic alpha-2-adrenoceptors in the hypothalamus. Neither saline nor the peripherally active PNMT inhibitor SKF29661 (50 mg/kg) increased hypothalamic MHPG. Both SKF64139 (50 mg/kg) and yohimbine (5 mg/kg) increased MHPG significantly when compared with SKF29661. There was no significant increase in MHPG after the administration of CGS19281A (20 mg/kg). Blood GH increased 30 min after clonidine was administered. While CGS19281A (20 mg/kg), SKF64139 (50 mg/kg) and yohimbine (5 mg/kg) inhibited GH secretion, the peripherally active PNMT inhibitor SKF29661 (50 mg/kg) did not. These results suggest that CGS19281A has an in vivo inhibitory effect on the clonidine induced GH secretion. This may be due to inhibition of adrenaline synthesis by this agent.