• Advances in Traditional Medicine
• /
• v.7 no.2
• /
• pp.182-190
• /
• 2007

Alzheimer's disease is a neurodegenerative disorder associated with a decline in cognitive abilities. Dementia is one of the aged related mental problems and a characteristic symptom of Alzheimer's disease. Nootropic agents like piracetam and cholinesterase inhibitors like $Donepezil^{\circledR}$ are used in situations where there is organic disorder in learning abilities, but the resulting side-effects associated with these agents have limited their utility. Foeniculum (F.) vulgare Linn. is widely used in Indian traditional systems of medicines and also as a house remedy for nervous debility. The present work was undertaken to assess the potential of F. vulgare as a nootropic and anti-cholinesterase agent in mice. Exteroceptive behavioral models such as Elevated plus maze and Passive avoidance paradigm were employed to assess short term and long term memory in mice. To delineate the possible mechanism through which F. vulgare elicits the anti-amnesic effects, its influence on central cholinergic activity was studied by estimating the whole brain acetylcholinesterase activity. Pretreatment of methanolic extract of fruits of F. vulgare Linn. for 8 successive days, ameliorated the amnesic effect of scopolamine (0.4 mg/kg) and aging induced memory deficits in mice. F. vulgare extract significantly decreased transfer latencies of young mice and aged mice, increased step down latency and exhibited significant anti-acetyl cholinesterase effects, when compared to piracetam, scopolamine and control groups of mice. F. vulgare might prove to be a useful memory restorative agent in the treatment of dementia seen in the elderly.

• YAKHAK HOEJI
• /
• v.46 no.3
• /
• pp.185-191
• /
• 2002

Alzheimer's disease (AD) involves neuronal degeneration with impaired cholinergic transmission, particularly in areas of the brain associated with learning and memory. Several cholinesterase inhibitors are widely prescribed to ameliorate the cognitive deficits in AD patients. In an attempt to examine if tacrine and donepezil, two well-known cholinesterase inhibitors, exhibit additional pharmacological actions in primary cultured rat cortical cells, we investigated the effects on neuronal injuries induced by glutamate or N-methyl-D-aspartate (NMDA), $\beta$-amyloid fragment ( $A_{{beta}25-35)}$), and various oxidative insults. Both tacrine and donepezil did not significantly inhibit the excitotoxic neuronal damage induced by glutamate. However, tacrine inhibited the toxicity induced by NMDA in a concentration-dependent fashion. In addition, tacrine significantly inhibited the $A_{{beta}25-35)}$-induced neuronal injury at the concentration of 50 $\mu$M. In contrast, donepezil did not reduce the NMDA- nor $A_{{beta}25-35)}$-induced neuronal injury. Tacrine and donepezil had no effects on oxidative neuronal injuries in cultures nor on lipid peroxidation in vitro. These results suggest that, in addition to its anticholinesterase activity, the neuroprotective effects by tacrine against the NMDA- and $A_{{beta}25-35)$-induced toxicity may be beneficial for the treatment of AD. In contrast, the potent and selective inhibition of central acetylcholinesterase appears to be the major action mechanism of donepezil.

• Journal of The Korean Society of Clinical Toxicology
• /
• v.6 no.2
• /
• pp.83-90
• /
• 2008

Organophosphate (OP) pesticides are the most common source of human toxicity globally, causing high mortality and morbidity despite the availability of atropine as a specific antidote and oximes to reactivate acetylcholinesterase. The primary toxicity mechanism is inhibition of acetylcholinesterase (AchE), resulting in accumulation of the neurotransmitter, acetylcholine, and abnormal stimulation of acetylcholine receptors. Thus, the symptoms (muscarinic, nicotinic, and central nervous system) result from cholinergic overactivity because of AchE inhibition. OP can also cause rhabdomyolysis, pancreatitis, parotitis, and hepatitis. OP therapy includes decontamination, supportive therapy, and the use of specific antidotes such as atropine and oximes. However, there has been a paucity of controlled trials in humans. Here we evaluated the literature for advances in therapeutic strategies for acute OP poisoning over the last 10 years.

• The Korean Journal of Pain
• /
• v.33 no.4
• /
• pp.326-334
• /
• 2020

Background: In this study, we sought to evaluate whether systemic propentofylline (PPF) has antiallodynic effects in a rat model of postoperative pain, and to assess the mechanism involved. Methods: After plantar incision, rats were intraperitoneally injected with various doses of PPF to evaluate its antiallodynic effect. To investigate the involved mechanism, rats were intraperitoneally injected with yohimbine, dexmedetomidine, prazosin, naloxone, atropine or mecamylamine, following the incision of the rat hind paws, and then PPF was administered intraperitoneally. The mechanical withdrawal threshold (MWT) was evaluated using von Frey filaments at various time points and serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were measured to determine the inflammatory response level. Results: MWT was significantly increased after intraperitoneal injection of 30 mg/kg of PPF when compared with the control group. Injection of PPF and yohimbine, atropine or mecamylamine showed significant decreases in the MWT, while injection of PPF and dexmedetomidine showed a significant increase. Systemic administration of PPF inhibited the post-incisional increase in serum level of TNF-α and IL-1β. Conclusions: Systemic administration of PPF following surgery presented antiallodynic effects in a rat model of postoperative pain. The antiallodynic effects against mechanical allodynia could be mediated by α-adrenergic and cholinergic receptors.

• The Journal of Korean Academy of Sensory Integration
• /
• v.13 no.2
• /
• pp.75-84
• /
• 2015

Objective : The aim of this study was to provide mechanism information of a link between arousal and sensory modulation to increase understanding of neurophysiological study. Subject : Optimal arousal state of a child is an important issue in sensory integration therapy. Limbic system and reticular formation are related to sensory modulation by sensory input. Sensory inputs processes from reticular formation to cortex via ascending reticular activation system for moderate arousal. A lot of neurotransmitters such as cholinergic neurons and monoamin neurons help this processes. Mechanism of arousal was measured by functions of central nervous system (CNS) and autonomic nervous system (ANS) using objective tools such as an electroencephalogram (EEG) and electrodermal responses. Functions of CNS and ANS showed differences between normal children and children with disabilities. Optimal sensory input using sensory integration therapy for children with disabilities helps to act reticular formation, limbic system, and cortex and to maintain appropriate arousal. Conclusion : Such quantitative studies by using neurophysiological methods provide evidence for sensory integration therapy.

• The Korean Journal of Physiology and Pharmacology
• /
• v.14 no.5
• /
• pp.311-316
• /
• 2010

It is well-known that electrical field stimulation (EFS)-induced contraction is mediated by a cholinergic mechanism and other neurotransmitters. NO, ATP, calcitonin gene-related peptide (CGRP), and substance P are released by EFS. To investigate the purinergic mechanism involved in the EFS-induced contraction, purinegic receptors antagonists were used. Suramine, a non-selective P2 receptor antagonist, reduced the contraction induced by EFS. NF023 ($10^{-7}{\sim}10^{-4}M$), a selective P2X antagonist, inhibited the contraction evoked by EFS. Reactive blue ($10^{-6}{\sim}10^{-4}M$), selective P2Y antagonist, also blocked the contraction in a dose-dependent manner. In addition, P2X agonist ${\alpha}$,${\beta}$-methylene 5'-adenosine triphosphate (${\alpha}{\beta}MeATP$, $10^{-7}{\sim}10^{-5}M$) potentiated EFS-induced contraction in a dose-dependent manner. P2Y agonist adenosine 5'-[${\beta}$-thio]diphosphate trilithium salt ($ADP{\beta}S$, $10^{-7}{\sim}10^{-5}M$) also potentiated EFS-induced contractions in a dose-dependent manner. Ecto-ATPase activator apyrase (5 and 10 U/ml) reduced EFS-induced contractions. Inversely, 6-N,$N$-diethyl-D-${\beta}$,${\gamma}$- dibromomethylene 5'-triphosphate triammonium (ARL 67156, $10^{-4}M$) increased EFS-induced contraction. These data suggest that endogenous ATP plays a role in EFS-induced contractions which are mediated through both P2X-receptors and P2Y-receptors stimulation in cat esophageal smooth muscle.

• The Korean Journal of Physiology and Pharmacology
• /
• v.7 no.4
• /
• pp.231-238
• /
• 2003

The present study was undertaken to investigate the effect of bradykinin on secretion of catecholamines (CA) evoked by stimulation of cholinergic receptors and membrane depolarization from the isolated perfused model of the rat adrenal glands, and to elucidate its mechanism of action. Bradykinin $(3{\times}10^{-8}M)$ alone produced a weak secretory response of the CA. however, the perfusion with bradykinin $(3{\times}10^{-8}M)$ into an adrenal vein of the rat adrenal gland for 90 min enhanced markedly the secretory responses of CA evoked by ACh $(5.32{\times}10^{-3}M)$, excess $K^+$ ($5.6{\times}10^{-2}M$, a membrane depolarizer), DMPP ($10^{-4}$ M, a selective neuronal nicotinic agonist) and McN-A-343 ($10^{-4}$ M, a selective M1-muscarinic agonist). Moreover, bradykinin ($3{\times}10^{-8}$ M) in to an adrenal vein for 90 min also augmented the CA release evoked by BAY-K-8644, an activator of the dihydropyridine L-type $Ca^{2+}$ channels. However, in the presence of $(N-Methyl-D-Phe^7)$-bradykinin trifluoroacetate salt $(3{\times}10^{-8}M)$, an antagonist of $BK_2$-bradykinin receptor, bradykinin no longer enhanced the CA secretion evoked by Ach and high potassium whereas the pretreatment with Lys-$(des-Arg^9,\;Leu^9)$-bradykinin trifluoroacetate salt $(3{\times}10^{-8}M)$, an antagonist of $BK_1$-bradykinin receptor did fail to affect them. Furthermore, the perfusion with bradykinin $(3{\times}10^{-6}M)$ into an adrenal vein of the rabbit adrenal gland for 90 min enhanced markedly the secretory responses of CA evoked by excess $K^+$ $(5.6{\times}10^{-2}M)$. Collectively, these experimental results suggest that bradykinin enhances the CA secretion from the rat adrenal medulla evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) and membrane depolarization through the activation of $B_2$-bradykinin receptors, not through $B_1$-bradykinin receptors. This facilitatory effect of bradykinin seems to be associated to the increased $Ca^{2+}$ influx through the activation of the dihydropyridine L-type $Ca^{2+}$ channels.

• The Korean Journal of Physiology and Pharmacology
• /
• v.13 no.3
• /
• pp.229-239
• /
• 2009

The aim of the present study was to examine the effect of provinol, which is a mixture of polyphenolic compounds from red wine, on the secretion of catecholamines (CA) from isolated perfused rat adrenal medulla, and to elucidate its mechanism of action. Provinol (0.3 ${\sim}$ 3 ${\mu}g/ml$) perfused into an adrenal vein for 90 min dose- and time-dependently inhibited the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (a direct membrane-depolarizer, 56 mM), DMPP (a selective neuronal nicotinic $N_N$ receptor agonist, 100 ${\mu}M$) and McN-A-343 (a selective muscarinic $M_1$ receptor agonist, 100 ${\mu}M$). Provinol itself did not affect basal CA secretion. Also, in the presence of provinol (1 ${\mu}g/ml$), the secretory responses of CA evoked by Bay-K-8644 (a voltage-dependent L-type dihydropyridine $Ca^{2+}$ channel activator, 10 ${\mu}M$), cyclopiazonic acid (a cytoplasmic $Ca^{2+}$-ATPase inhibitor, 10 ${\mu}M$) and veratridine (an activator of voltage-dependent $Na^+$ channels, 10 ${\mu}M$) were significantly reduced. Interestingly, in the simultaneous presence of provinol (1 ${\mu}g/ml$) plus L-NAME (a selective inhibitor of NO synthase, 30 ${\mu}M$), the CA secretory responses evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyclpiazonic acid recovered to the considerable extent of the corresponding control secretion in comparison with the inhibition of provinol-treatment alone. Under the same condition, the level of NO released from adrenal medulla after the treatment of provinol (3 ${\mu}g/ml$) was greatly elevated in comparison to its basal release. Taken together, these data demonstrate that provinol inhibits the CA secretory responses evoked by stimulation of cholinergic (both muscarinic and nicotinic) receptors as well as by direct membrane-depolarization from the perfused rat adrenal medulla. This inhibitory effect of provinol seems to be exerted by inhibiting the influx of both calcium and sodium into the rat adrenal medullary cells along with the blockade of $Ca^{2+}$ release from the cytoplasmic calcium store at least partly through the increased NO production due to the activation of nitric oxide synthase.

• The Korean Journal of Pharmacology
• /
• v.27 no.2
• /
• pp.167-181
• /
• 1991

The present study was an attempt to investigate the effect of forskolin on secretion of catecholamines (CA) evoked by Ach, excess $K^+$, DMPP, McN-A-343 and caffeine from the isolated perfused rat adrenal glands and to elucidate its mechanism of action. The perfusion with forskolin (1.0 uM) for 1 min into the adrenal vein enhanced markedly the secreation of CA evoked by Ach (50 ug), excess $K^+$ (56 mM) DMPP (100 uM) and by caffeine (0.3 mM) but did not that by McN-A-343. Forskolin alone did not potentiate the CA secretion. Moreover, forskolin augmented the CA release evoked by the above same stimulation even in the absence of extracellular calcium. The 1 min perfusion of 300 uM-dibutyryl cyclic AMP (DBcAMP), which is known to increase cyclic AMP levels, led to enhancement of Ca secretion evoked by Ach, excess $K^+$ and DMPP but did not that by McN-A-343 and caffeine. DBcAMP by itself also did not augment the CA secretion. In the calcium-free medium DBcAMP significantly enhanced the CA secretion by the same stimulation, except for the case of McN-A-343. These experimental results suggest that forskolin activates adenylate cyclase, resulting the elevation of cyclic AMP which may potentiate cholinergic nicotinic receptor-mediated and also depolarization-dependent CA secretion and that it may alter the intracellular calcium homeostasis in the rat adrenal glands.

• The Korean Journal of Physiology and Pharmacology
• /
• v.12 no.4
• /
• pp.155-164
• /
• 2008

Resveratrol has been known to possess various potent cardiovascular effects in animal, but there is little information on its functional effect on the secretion of catecholamines (CA) from the perfused model of the adrenal medulla. Therefore, the aim of the present study was to determine the effect of resveratrol on the CA secretion from the isolated perfused model of the normotensive rat adrenal gland, and to elucidate its mechanism of action. Resveratrol (10${\sim}100{\mu}$M) during perfusion into an adrenal vein for 90 min inhibited the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (a direct membrane-depolarizer, 56 mM), DMPP (a selective neuronal nicotinic $N_n$ receptor agonist, 100${\mu}$M) and McN-A-343 (a selective muscarinic $M_1$ receptor agonist, 100${\mu}$M) in both a time- and dose- dependent fashion. Also, in the presence of resveratrol (30${\mu}$M), the secretory responses of CA evoked by veratridine 8644 (an activator of voltage-dependent$Na^+$ channels, 100${\mu}$M), Bay-K-8644 (a L-type dihydropyridine $Ca^{2+}$ channel activator, 10${\mu}$M), and cyc1opiazonic acid (a cytoplasmic $Ca^{2+}$-ATPase inhibitor, 10${\mu}$M) were significantly reduced. In the simultaneous presence of resveratrol (30${\mu}$M) and L-NAME (an inhibitor of NO synthase, 30${\mu}$M), the CA secretory evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyc1opiazonic acid were recovered to a considerable extent of the corresponding control secretion compared with the inhibitory effect of resveratrol alone. Interestingly, the amount of nitric oxide (NO) released from the adrenal medulla was greatly increased in comparison to its basal release. Taken together, these experimental results demonstrate that resveratrol can inhibit the CA secretory responses evoked by stimulation of cholinergic nicotinic receptors, as well as by direct membrane-depolarization in the isolated perfused model of the rat adrenal gland. It seems that this inhibitory effect of resveratrol is exerted by inhibiting an influx of both ions through $Na^+$ and $Ca^{2+}$ channels into the adrenomedullary cells as well as by blocking the release of $Ca^{2+}$ from the cytoplasmic calcium store, which are mediated at least partly by the increased NO production due to the activation of NO synthase.