Central inhibitory effect of scopolamine and its adrenergic antagonistic activity
Abstract
Following an intracerebroventricular injection (icv) of scopolamine 10 mg in rabbits, the righting reflex disappeared for 81+/-(SD) 4 min. The combined use of scopolamine with adrenaline (100 microg), isoprenaline (100 microg) or neosynephrine (2 mg) shortened the durations of loss of righting reflex: 21+/-5, 19+/-4, and 21+/-4 min, respectively (P<0.01). Meantime, the central inhibitory effect of scopolamine became less marked.
A gradual EEG change from low voltage rapid wave to high voltage slow wave was observed on rabbits after icv scopolamine 0.2 mg, with the peak action in 15 min and the duration lasting about 6 h. Additional icv adrenaline or isoprenaline (100 microg) given 15 min later produced a low voltage rapid wave for 3-10 min, while additional neosynephrine 0.5 mg produced a similar effect only in 3 out of 10 rabbits. As the dosage of scopolamine was increased to 1 mg, the additional adrenomimetics no longer showed such arousal reactions.
When scopolamine 10 mg and phentolamine 1 mg were introduced icv separately into the same rabbit, the loss of righting reflex was significantly prolonged to 72+/-16 min (P<0.01). Icv scopolamine (0.1 mg) or phentolamine (0.5 mg) alone induced an EEG change to high voltage low frequency intermittently; while the combination of these 2 drugs produced an EEG completely of high voltage slow wave, the voltage being higher than that obtained in rabbits receiving either of the two drugs. This suggested the presence of a synergistic action between them. However, combination of scopolamine with beta-adrenoceptor blocking agents (propranolol and practolol) yielded no synergistic action.
These results showed that scopolamine could antagonize adrenomimetics in their central effects, and suggested that the central inhibitory effects of scopolamine should be related to the alpha-, not the beta-, adrenoceptor blocking action.
Keywords:
A gradual EEG change from low voltage rapid wave to high voltage slow wave was observed on rabbits after icv scopolamine 0.2 mg, with the peak action in 15 min and the duration lasting about 6 h. Additional icv adrenaline or isoprenaline (100 microg) given 15 min later produced a low voltage rapid wave for 3-10 min, while additional neosynephrine 0.5 mg produced a similar effect only in 3 out of 10 rabbits. As the dosage of scopolamine was increased to 1 mg, the additional adrenomimetics no longer showed such arousal reactions.
When scopolamine 10 mg and phentolamine 1 mg were introduced icv separately into the same rabbit, the loss of righting reflex was significantly prolonged to 72+/-16 min (P<0.01). Icv scopolamine (0.1 mg) or phentolamine (0.5 mg) alone induced an EEG change to high voltage low frequency intermittently; while the combination of these 2 drugs produced an EEG completely of high voltage slow wave, the voltage being higher than that obtained in rabbits receiving either of the two drugs. This suggested the presence of a synergistic action between them. However, combination of scopolamine with beta-adrenoceptor blocking agents (propranolol and practolol) yielded no synergistic action.
These results showed that scopolamine could antagonize adrenomimetics in their central effects, and suggested that the central inhibitory effects of scopolamine should be related to the alpha-, not the beta-, adrenoceptor blocking action.