• Biomolecules & Therapeutics
• /
• 제1권1호
• /
• pp.1-8
• /
• 1993

It has been known that calcium antagonists also inhibit the radioligand binding to muscarinic and $\alpha$-adrenergic receptors and, in case of verapamil, these inhibitions may play a role in the effects of verapamil on the heart. In this study, the effects of nicardipine, nifedipine, nimodipine, diltiazem and verapamil on the binding of [$^3H$]dihydroalprenolol (DHA) to dog cardiac ${\beta}$-adrenergic receptors were examined. A single uniform [$^3H$]DHA binding site ($K_D/= 5nM\;and\;B_{max}=2600$ fmol/mg protein) was identified in dog cardiac sarcolemma. [$^3H$]DHA binding was not affected by the usual therapeutic concentrations of these calcium antagonists (nanomolar range) but in the "nonspecific"concentration ranges ($28-180{\mu}m$) these drugs inhibited [$^3H$]DHA binding to $\beta$-adrenergic receptors. Nicardipine, nifedipine, nimodipine and diltiazem competed for [$^3H$]DHA binding to ${\beta}$-adrenergic receptors with dissociation constants ($K_i$) of $28{\mu}m,\' 74{\mu}m, 39{\mu}m \;and \;35{\mu}m,$ respectively. Verapamil ($K_i=176.5 {\mu}m$) was less potent inhibitor than other drugs and this inhibition was noncompetitive; the maximal binding capacity ($B_{max}$) $300 {\mu}m$ verapamil without change in the apparent dissociation constant (4K_D$) for DHA. These results indicate that the inhibitory action of calcium antagonists at high concentrations on ${\beta}$-adrenergic receptors is not involved in the therapeutic effects of these drugs by the calcium channel blocking action.

• 대한수의학회지
• /
• 제24권1호
• /
• pp.17-23
• /
• 1984

To validate the physiological properties of the histamine receptors of ileal smooth muscle in dog, the effects of adrenergic-, cholineric-, and H-receptor antagonists on the responses of ileal smooth muscle strips to histamine were investigated. The results were summarized as follows; 1. Histamine caused the contraction of ileal smooth muscle and the contractile responses were increased between the concentration of histamine $10^{-7}M$ and $10^{-5}M$ with dose-dependent manner in dog. 2. The shorter the treatment interval of histamine, the lower the contractile activity until the treatment interval extended to 40 minutes. 3. The contractile response induced by histamine was completely blocked by the pre treatment with a $H_1$-receptor blocker, chlorpheniramine and not by the pretreatment with a $H_2$-receptor blockers cimetidine. 4. The contractile response induced by histamine was not blocked by the pretreatment with a cholinergic receptor blocker, atropine. 5. The contractile response induced by histamine was not blocked by the pretreatment with an ${\alpha}$-adrenergic receptor blocker, phenoxybenzamine, or a ${\beta}$-adrenergic receptor blocker, propranolol. From these results, it was suggested that the contraction induced by histamine was elicited through $H_1$-receptor on the ileal smooth muscle in dog.

• The Korean Journal of Physiology and Pharmacology
• /
• 제2권6호
• /
• pp.753-761
• /
• 1998

Preconditioning of a heart with small doses of catecholamines induces a tolerance against the subsequent lethal ischemia. The present study was performed to find a specific receptor pathway involved with the catecholamine preconditioning and to test if adenosine plays a role in this cardioprotective effect. Isolated rat hearts, pretreated with small doses of ${\alpha}-\;or\;{\beta}-adrenergic$ agonists/antagonists, were subjected to 20 minutes ischemia and 20 minutes reperfusion by Langendorff perfusion method. Cardiac mechanical functions, lactate dehydrogenase and adenosine release from the hearts were measured before and after the drug treatments and ischemia. In another series of experiments, adenosine $A_1\;or\;A_2$ receptor blockers were treated prior to administration of adrenergic agonists. Pretreatments of a ${\beta}-agonist,\;isoproterenol(10^{-9}{\sim}10^{-7}\;M)$ markedly improved the post-ischemic mechanical function and reduced the lactate dehydrogenase release. Similar cardioprotective effect was observed with an ?-agonist, phenylephrine pretreatment, but much higher $concentration(10^{-4}\;M)$ was needed to achieve the same degree of cardioprotection. The cardioprotective effects of isoproterenol and phenylephrine pretreatments were blocked by a ${\beta}_1-adrenergic$ receptor antagonist, atenolol, but not by an ${\alpha}_1-antagonist,$ prazosin. Adenosine release from the heart was increased by isoproterenol, and the increase was also blocked by atenolol, but not by prazosin. A selective $A_1-adenosine$ receptor antagonist, 1,3-dipropyl-8-cyclopentyl xanthine (DPCPX) blocked the cardioprotection by isoproterenol pretreatment. These results suggest that catecholamine pretreatment protects rat myocardium against ischemia and reperfusion injury by mediation of ${\beta}_1-adrenergic$ receptor pathway, and that adenosine is involved in this cardioprotective effect.

• 대한약리학회지
• /
• 제22권1호
• /
• pp.24-33
• /
• 1986

본 연구에서는 개구리(Rana nigromaculata)의 피부에 있어서 전위차(PD), 단락전류(SCC) 및 total skin conductance(TSC)에 미치는 제종 adrenergic agonist 및 그 차단제의 영향을 관찰하여 개구리 피부에 adrenoceptors의 존재를 확인하고 Na 수송에 있어 그들의 역할을 구명코자 하였다. 1.Norepinephrine(NE, $6{\times}10^{-8}-6{\times}10^{-5}M$), phenylephrine($PE,5{\times}10^{-6}-5{\times}10^{-4}M$)의 PD 및 epinephrine(Epi, $5.5{\times}10^{-7}-5.5{\times}10^{-5}M$)의 PD 및 SCC 증가효과는 약물의 투여농도에 비례하였으며, Epi의 최대효과는 NE나 PE의 것보다 약하였다. 2. 이러한 PD 및 SCC의 증가효과는 alpha 1 adrenoceptor 차단체인 prazosin $2{\times}10^{-6}M$에 의해서 억제되었으며, 특히 Epi의 증가효과는 불가역성 alpha receptor 차단제인 phenoxybenzamine $3.3{\times}10^{-5}M$에 의하여 완전히 차단되며 대량의 Epi에 의해서는 PD 및 SCC의 감소를 초래하였다. 3. Beta adrenoceptor agonist인 isoproterenol$(5{\times}10^{-7}-5{\times}10^{-6}M)$에 의해 농도증가에 비례한 PD 및 SCC의 감소가 일어났으며, 이는 선택적 bete receptor 차단제인 propranolol $4{\times}10^{-6}M$에 의해 차단되었다. 또한 Epi의 PD 및 SCC 증가효과는 propranolol $4{\times}10M$에 의하여 강화됨을 볼 수 있었다. 4. Alpha 2 adrenoceptor agonist인 clonidine 및 guanabenz도 PD 및 SCC의 증가를 가져왔으며 이러한 효과는 alpha 2 receptor 차단제인 yohimbine에서 보다 Alpha 1 receptor 차단제인 prazosin에 의해 더 잘 억제되었다. 이상 실험의 결과 개구리 복부피부에도 포유동물에서와 같이 adrenergic alpha 및 beta receptor가 존재하며 alpha receptor는 PD 및 SCC의 증가를, beta receptor는 PD 및 SCC의 감소를 매개하여, 개구리 피부의 Na 수송에 있어 adrenergic system이 중요한 조절작용을 하고 있음을 알 수 있었다. 그러나 여기에 관여하는 alpha receptor는 다른 포유류에서와 같이 alpha 1 및 alpha 2 adrenoceptor로 구분할 수는 없었다.

• The Korean Journal of Pain
• /
• 제24권4호
• /
• pp.179-184
• /
• 2011

Background: The analgesic mechanisms of cyclooxygenase (COX)-2 inhibitors have been explained mainly on the basis of the inhibition of prostaglandin biosynthesis. However, several lines of evidence suggest that their analgesic effects are mediated through serotonergic or adrenergic transmissions. We investigated the roles of these neurotransmitters in the antinociception of a selective COX-2 inhibitor at the spinal level. Methods: DUP-697, a selective COX-2 inhibitor, was delivered through an intrathecal catheter to male Sprague-Dawley rats to examine its effect on the flinching responses evoked by formalin injection into the hindpaw. Subsequently, the effects of intrathecal pretreatment with dihydroergocristine, prazosin, and yohimbine, which are serotonergic, ${\alpha}1$ adrenergic and ${\alpha}2$ adrenergic receptor antagonists, respectively, on the analgesia induced by DUP-697 were assessed. Results: Intrathecal DUP-697 reduced the flinching response evoked by formalin injection during phase 1 and 2. But, intrathecal dihydroergocristine, prazosin, and yohimbine had little effect on the antinociception of intrathecal DUP-697 during both phases of the formalin test. Conclusions: Intrathecal DUP-697, a selective COX-2 inhibitor, effectively relieved inflammatory pain in rats. Either the serotonergic or adrenergic transmissions might not be involved in the analgesic activity of COX-2 inhibitors at the spinal level.

• 셀메드
• /
• 제2권4호
• /
• pp.38.1-38.6
• /
• 2012

The present study aimed to determine the possible mechanisms of the peripheral antinociception of the aqueous extracts of Dicranopteris linearis (AEDL), Melastoma malabathricum (AEMM) and Bauhinia purpurea (AEBP) leaves in mice. Briefly, the antinociceptive profile of each extract (300, 500, and 1000 mg/kg; subcutaneous (s.c.)), was established using the abdominal constriction test. A single dose (500 mg/kg) of each extract (s.c.) was pre-challenged for 10 min with various pain receptors' antagonists or pain mediators' blockers and 30 min later subjected to the antinociceptive assay to determine the possible mechanism(s) involved. Based on the results obtained, all extracts exerted significant (p < 0.05) antinociceptive activity with dose-dependent activity observed only with the AEMM. Furthermore, the antinociception of AEDL was attenuated by naloxone, atropine, yohimbine and theophylline; AEMM was reversed by yohimbine, theophylline, thioperamide, pindolol, reserpine, and 4-chloro-DL-phenylalanine methyl ester hydrochloride; and of AEBP was inhibited by naloxone, haloperidol, yohimbine and reserpine. In conclusion, the antinociceptive activity of those extracts possibly involved the activation of several pain receptors (i.e. opioids, muscarinic, ${\alpha}_2$-adrenergic and adenosine receptors, adenosine, H3-histaminergic and $5HT_{1A}$, dopaminergic receptors).

• The Korean Journal of Pain
• /
• 제32권1호
• /
• pp.3-11
• /
• 2019

Going back to basics prior to mentioning the use of antipsychotics in patients with pain, the International Association for the Study of Pain (IASP) definition of pain can be summarized as an unpleasant experience, composed of sensory experience caused by actual tissue damage and/or emotional experience caused by potential tissue damage. Less used than antidepressants, antipsychotics have also been used for treating this unpleasant experience as adjuvant analgesics without sufficient evidence from research. Because recently developed atypical antipsychotics reduce the adverse reactions of extrapyramidal symptoms, such as acute dystonia, pseudo-parkinsonism, akathisia, and tardive dyskinesia caused by typical antipsychotics, they are expected to be used more frequently in various painful conditions, while increasing the risk of metabolic syndromes (weight gain, diabetes, and dyslipidemia). Various antipsychotics have different neurotransmitter receptor affinities for dopamine (D), 5-hydroxytryptamine (5-HT), adrenergic (${\alpha}$), histamine (H), and muscarinic (M) receptors. Atypical antipsychotics antagonize transient, weak $D_2$ receptor bindings with strong binding to the $5-HT_{2A}$ receptor, while typical antipsychotics block long-lasting, tight $D_2$ receptor binding. On the contrary, antidepressants in the field of pain management also block the reuptake of similar receptors, mainly on the 5-HT and, next, on the norepinephrine, but rarely on the D receptors. Antipsychotics have been used for treating positive symptoms, such as delusion, hallucination, disorganized thought and behavior, perception disturbance, and inappropriate emotion, rather than the negative, cognitive, and affective symptoms of psychosis. Therefore, an antipsychotic may be prescribed in pain patients with positive symptoms of psychosis during or after controlling all sensory components.

• The Korean Journal of Pain
• /
• 제13권2호
• /
• pp.156-163
• /
• 2000

Background: Peripheral nerve injury sometimes leads to chronic neuropathic pain such as causalgia. A subset of patients with causalgia have a sympathetically maintained pain which is often evoked by cooling stimuli. However, our knowledge on adrenergic receptor types responsible for cold-evoked pain that is sympathetically dependent is lacking. The present study was conducted to investigate subtypes of adrenoceptors involved in mediating cold-evoked pain that developed following peripheral nerve injury. Methods: Neuropathic surgery was performed by a unilateral ligation of L5 and L6 spinal nerves of rats. Behavioral sign of cold-evoked pain was examined for 5 min by measuring cumulative duration of time that the rat lifted its foot off a metal plate held at cold temperature ($5^{\circ}C$). Whether cold-evoked pain behavior was affected by antagonists of various subtypes of adrenoceptors, which were administered intraperitoneally before and after the ligation, was investigated. Results: After ligation, duration of foot lifting on the ligated side at cold temperature increased as compared to the pre-operative period. This increase maintained for the entire 40-day test period. Pretreatment with alpha-antagonist phentolamine produced a suppression of cold-evoked pain behavior that was not affected by beta-antagonist propranolol pretreatment. Prazosin, alpha-1 antagonist, suppressed cold- evoked pain behavior when treated either before or after nerve ligation. On the other hand, alpha-2 antagonist yohimbine was without effect on cold-evoked pain behavior whether it was treated before or after the ligation. Conclusions: The results suggest that peripheral nerve injury develops cold-evoked pain that is sympathetically dependent, and that alpha-1 adrenoreceptor plays a critical role for the generation of this type of pain in its initiation as well as maintenance.

• International Neurourology Journal
• /
• 제22권4호
• /
• pp.252-259
• /
• 2018

Purpose: Naftopidil ((${\pm}$)-1-[4-(2-methoxyphenyl) piperazinyl]-3-(1-naphthyloxy) propan-2-ol) is prescribed in several Asian countries for lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Previous animal experiments showed that intrathecal injection of naftopidil abolished rhythmic bladder contraction in vivo. Naftopidil facilitated spontaneous inhibitory postsynaptic currents in substantia gelatinosa (SG) neurons in spinal cord slices. These results suggest that naftopidil may suppress the micturition reflex at the spinal cord level. However, the effect of naftopidil on evoked excitatory postsynaptic currents (EPSCs) in SG neurons remains to be elucidated. Methods: Male Sprague-Dawley rats at 6 to 8 weeks old were used. Whole-cell patch-clamp recordings were made using SG neurons in spinal cord slices isolated from adult rats. Evoked EPSCs were analyzed in $A{\delta}$ or C fibers. Naftopidil or prazosin, an ${\alpha}1$-adrenoceptor blocker, was perfused at $100{\mu}M$ or $10{\mu}M$, respectively. Results: Bath-applied $100{\mu}M$ naftopidil significantly decreased the peak amplitudes of $A{\delta}$ and C fiber-evoked EPSCs to $72.0%{\pm}7.1%$ (n=15) and $70.0%{\pm}5.5%$ (n=20), respectively, in a reversible and reproducible manner. Bath application of $100{\mu}M$ prazosin did not inhibit $A{\delta}$ or C fiber-evoked EPSCs. Conclusions: The present study suggests that a high concentration of naftopidil reduces the amplitude of evoked EPSCs via a mechanism that apparently does not involve ${\alpha}1$-adrenoceptors. Inhibition of evoked EPSCs may also contribute to suppression of the micturition reflex, together with nociceptive stimulation.

• Advances in Traditional Medicine
• /
• 제6권3호
• /
• pp.186-195
• /
• 2006

The present study was carried out to determine the involvement of opioid and non-opioid receptor and the effect of pH and enzymes on the recently reported antinociceptive activity of aqueous extract of Corchorus olitorius (AECO) leaves using the abdominal constriction test. The extract was prepared by soaking the dried powdered leaves of Corchorus (C.) olitorius in distilled water overnight, and the supernatant obtained was considered as a stock solution with 100% concentration/ strength. The extract, administered subcutaneously in the concentrations/ strength of 10, 50 and 100%, was found to show a significant concentration-independent antinociception. The 50% concentration AECO were further used to study on the above mentioned parameters. The extract exhibited: significant (P < 0.05) decreased in activity when pre-treated (s.c.) against 10 mg/kg naloxonazine, bicuculine (10 mg/kg), phenoxybenzamine (10 mg/kg), 10 mg/kg pindolol, and 5 mg/kg mecamylamme, but not 10 mg/kg naltrindole, 10 mg/kg atropine, respectively; significant (P < 0.05) decreased in activity after pre-treatment against 10% a-amylase, but not 1 % protease or 10% lipase and; significant (P < 0.05) decreased in activity after exposure to alkaline condition (pH between 9 and 13) while maintaining the activity at acidic condition, respectively. The C. olitorius leaves antinociception, which involved, at least in part, activation of $\mu-opioid,\;\alpha-and\;\beta-adrenergic$, and nicotinic receptors, was found to decrease under alkaline condition and in the presence of $\alpha-amylase$.