• 대한약리학회지
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• 제28권1호
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• pp.11-18
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• 1992

Physostigmine을 급성(0.75 mg/kg), 7일간 매일 1회(0.75 mg/kg) 그리고 7일간 연속(0.15 mg/kg/h) 투여한 쥐의 선조체에 있어서 dopamine(DA) 및 대사체와 tyrosine hydroxylase(TH)활성도의 변화를 검색하였다. 급성 투여 1시간 후 선조체의 DA 농도는 변화가 없었으나 dihydroxy-phenylacetic acid(DOPAC)과 homovanillic acid(HVA)농도는 증가하였다. 또한 DA의 turnover의 증가를 제시하는 DOPAC/DA와 HVA/DA의 비율도 증가하였다. 그러나 TH활성도는 24시간 후 감소를 나타내었다. Physostigmine을 매일 및 연속 투여군에서는 DA과 대사체의 농도에는 변화가 없었으나, DA의 turnover의 감소를 제시하는 DA과 대사체의 비율은 감소하였다. 그러나 TH활성도는 매일 투여군에서만 감소를 나타내었다. 이러한 결과는 physostigmine을 급성 및 아급성으로 투여시 dopamine대사의 변화가 있음을 제시한다. 또한 콜린 신경계의 아급성 자극은 dopamine 대사 및 활성도를 감소 시킬 가능성을 시사해 주었다.

• Animal cells and systems
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• 제16권3호
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• pp.198-206
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• 2012

Anxiety in zebrafish can be determined by examining their bottom-dwelling and light-avoidance behavior. This study determines the effects of physostigmine and scopolamine on anxiety in zebrafish by measuring swimming frequency for three horizontal layers and three vertical columns of a water test tank illuminated by a light source located above the central surface of the tank. In the 1 h session, zebrafish in the control group preferred the bottom layer the most and the center column the least. Zebrafish treated with 2-20 ${\mu}M$ physostigmine were more likely to prefer the to layer than controls, and there were significant pairwise differences between physostigmine-treated zebrafish and controls, indicating the anxiolytic effect of physostigmine. Further, 10 and $20{\mu}M$ physostigmine-treated zebrafish no longer avoided the center column. Scopolamine had no anxiolytic effect on bottom-dwelling and light-avoidance behaviors but suppressed the anxiolytic effect of physostigmine. In terms of their preference for various zones formed by layers and columns, zebrafish in the control group preferred the bottom left and right zones the most. Physostigmine had a positive effect on the preference for the top center zone, which was suppressed by scopolamine pretreatment. The results suggest that the level of anxiety in zebrafish can be reduced by activating acetylcholinergic neurotransmitter systems, which is mediated in part by muscarinic receptors.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Current Trends in Toxicological Sciences
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• pp.123-123
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• 2002

Abstract The protective effects of physostigmine against the toxicity of parathion (diethyl-4-nitrophenyl phosphorothionate) were examined in male Sprague-Dawley rats. Physostigmine (100 or 1,000 ㎎/㎏, ip) injected 30 min before decreased the inhibition of acetylcholinesterase (AChE) activities in brain, lung and blood induced by parathion (2 ㎎/㎏, ip).(omitted)

• Toxicological Research
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• 제16권3호
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• pp.195-200
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• 2000

Antidotal efficacy of physostigmine plus procyclidine, the combinational prophylactics for organophosphate poisoning, was evaluated in rats and guinea pigs. To assess the dose-response relation-ship in rats, various doses (0.3-6.0mg/kg) of procyclidine in combination with a fixed dose (0.1mg/kg) of physostigmine were pretreated subcutaneously 30 min prior to subcutaneous exposure to nerve-agents. Physostigmine alone exerted protection ratios of 2.44, 1.20, 1.50, 1.50 and 2.20 folds for tabun, sarin, soman, cyclosarin and V-agent, respectively. Interestingly, coadmnistration of procyclidine with physostigmine exhibited remarkable synergistic effects in a dose-dependent manner, leading to 4.00~8.00 folds for tabun, 2.15-8.50 folds for sarin, 1.92~507 folds for so man, 2.15~2.90 folds for cyclosarin, and 2.71~10.50 folds for V-agent. On the contrary, a low effect (l.65 fold) was achieved with the traditional antidotes atropine (17.4 mg/kg) plus 2-pralidoxime (30 mg/kg) treated immediately after soman poisoning. Noteworthy, the combinational prophylactics markedly potentiated the effect of atropine plus 2-pralidoxime to 6.13 and 12.27 folds with 1.0 and 3.0 mg/kg of procyclidine, respectively, against soman poisoning. In guinea pigs, the physostigmine plus procyclidine prophylactics exerted protective effects of 3.00~4.70 folds against soman intoxcation, which were much higher at low doses (0.3~1.0 mg/kg) of procyclidine than those in rats. Taken together, it is proposed that the combinational prophylactics composed oj physostigmine and procyclidine could be a promising antidote regimen for the poisoning with organophosphates possessing diverse properties.

• Toxicological Research
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• 제8권1호
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• pp.71-81
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• 1992

Rats were treated with physostigamine acutely and subacutely for 7 days. The duration of tremor, striatal acetylcholinesterase(AChE) activity and the occurrences of dopaminal antagonist-induced catalepsy were measured. During the daily treatment with 0.75mg/kg of physostigmine, the durations of tremor were markedly reduced. However, the tremors were ot occurred in the continuous infusion up to 0.20mg/kg/hr. Striatal AChE activities were significantly inhibited(8.25%) early hour, but twenty-four hour after daily administration with physostigmine AChE activities during the continuous infusion with physostigmine were also significantly inhibites (30-60%).

• Journal of Chest Surgery
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• 제34권8호
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• pp.634-639
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• 2001

중추성 항콜린성 증후군(Central Anticholinergic Syndrome)은 중추신경계에서 콜린성 신경전달 활성도의 감소로 인하여 다양한 임상 양상을 보이는 질환이다. 이 증후군은 주로 마취시에 사용되는 약제와 연관되며 Physostigmine의 투여 후 증상이 반전되는 것으로 확진된다. 저자들은 뇌혈관 질환의 원인으로 생각되는 난원공 개존증에 대해 개심술을 시행한 후 발생한 중추성 항콜린성 증후군을 Physostigmine의 투여로 확진한 1례에 대하여 보고하는 바이다.

• 대한약리학회지
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• 제5권2호
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• pp.135-140
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• 1969

In order to investigate the effect of autonomic nervous system on salivary gland, the authors have observed the effects of various drugs acting on the autonomic nervous system to the rat submaxillary gland by comparing the changes of gland weight, the amylase activity and various electrolyte contents with control group. The results are as follows; 1. The pilocarpine, physostigmine, norepinephrine, atropine and DMPP increased the rat submaxillary gland weight. 2. The amylase activities of rat submaxillary gland were increased by pilocarpine, physostigmine and norepinephrine, but decreased by atropine and DMPP. 3. Calcium contents of rat submaxillary gland were highly increased by pilocarpine and physostigmine, hut slightly increased by norepinephrine. 4. Magnesium contents of rat submarillary gland were increased by DMPP, but decreased by pilocarpine, physostigmine and norepinephrine. 5. Sodium contents of rat subnaxillary gland were increased by pilocarpine, physostigmine, norepinephrine and DMPP, but decreased by atropine. 6. Potassium contents of rat submaxillary gland were highly increased by atropine, and slightly increased by DMPP and norepinephrine, but decreased by pilocarpine and physostigmine.

• Journal of Pharmaceutical Investigation
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• 제31권3호
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• pp.181-184
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• 2001

The purpose of this study was to develop transdermal drug delivery system (TDDS) for the combination of physostigmine and procyclidine. The effects of various pressure sensitive adhesives (PSA) on the percutaneous absorption of procyclidine across hairless mouse skin were evaluated to select an appropriate PSA. In addition, the influences of various vehicles on the percutaneous absorption of procyclidine from PSA matrix across hairless mouse skin were evaluated using flow-through diffusion cell system at $37^{\circ}C$. Physostigmine did not have any influence on the permeation rate of procyclidine. The flux of procyclidine was the highest in silicone and PIB and was relatively lower in SIS, Acryl, and SBS adhesive matrices, however, their use was limited by the crystallization of the drug in the matrix. Among acrylic adhesives, the permeability of procyclidine was the highest from poly (ethylene oxide) grafted acrylic adhesive. Some enhancers show different enhancing effect depending on the drug, however, many of the tested enhancers showed enhancing effect for the permeation of both procyclidine and physostigmine to some extent. $Crovol^{\circledR}$ EP 40 showed the highest enhancing effect on the permeation of both compounds. The size of TDDS to provide required permeation rate was estimated to be $35\;cm^2$ based on available information.

• Animal cells and systems
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• 제15권2호
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• pp.115-121
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• 2011

Previous studies have demonstrated that N-methyl-D-aspartate (NMDA) receptors and acetylcholine receptors are related to learning and memory in rat and mice. In this study, we examined the effects of MK-801, a non-competitive NMDA receptor antagonist, on learning and memory in zebrafish using a passive avoidance test. We further tested whether or not nicotine, a nicotinic acetylcholine receptor agonist, and physostigmine, an acetylcholinesterase inhibitor, reverse the effects of MK-801. Crossing time was increased significantly in the training and test sessions for the controls. When 20 ${\mu}M$ MK-801 was administered prior to the training session, the crossing time did not increase in either session. The MK-801-induced learning deficit was rescued by pretreatment with 20 ${\mu}M$ physostigmine, and crossing time was increased in the training and test sessions compared to the MK-801-treated zebrafish. Further, the MK-801-induced learning deficit was prevented by pretreatment with 20 ${\mu}M$ nicotine, and crossing time was increased in the training session but not in the test session. These results show that MK-801 induced a learning deficit in zebrafish that was prevented by pretreatment with nicotine and physostigmine.

• Toxicological Research
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• 제16권3호
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• pp.187-193
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• 2000

The antidotal, anticonvulsant and neuroprotective effects of physostigmine and procyclidine. the combinational prophylactics for organophosphate poisoning, were evaluated in rats. In comparison with a low protective effect (1.6 fold) of atropine (15 mg/kg) and 2-pralidoxime (30 mg/kg), the traditional antidotes regimen, a marked protection ratio of 7.3 fold was achieved by combinational pretreatment with physostigmine (0.05 mg/kg) and procyclidine (10 mg/kg), which was superior to that (3.5 fold) with pyri-dostigmine (0.1 mg/kg) and atropine (15 mg/kg). Rats exposed to a high dose (10 mg/kg. 2 X $LD_{50}$) of diisopropylfluorophosphate showed severe epileptiform seizures on electroencephalography, resulting in necrotic and apoptotic brain injuries in discrete brain regions under histopathological and TUNEL immuno-histochemical examinations in 24 hr. Such seizures and excitotoxic brain injuries were fully prevented by pretreatment with physostigmine (0.05 mg/kg) and procyclidine (10 mg/kg). in contrast to a negligible effect of pyridostigmine (0.1 mg/kg) and atropine (15 mg/kg). Taken together, it is proposed that the prophylactics composed of physostigmine and procyclidine could be a promising regimen for the prevention of lethality, seizures and brain injuries induced by organophosphate poisoning.