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Showa Ueki - One of the best experts on this subject based on the ideXlab platform.
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nootropic candidates inhibit head twitches induced by mescaline in mice
Japanese Journal of Pharmacology, 1992Co-Authors: Tsuneyuki Yamamoto, Shinichi Yatsugi, Yasuhiro Fujikawa, Masuo Ohno, Showa UekiAbstract:The effects of various nootropic candidates on mescaline-induced head-twitches were studied in mice. The number of head-twitches induced by mescaline (100 mg/kg, s.c.) was significantly reduced by idebenone (32 and 100 mg/kg, i.p.), Minaprine (0.32-10 mg/kg, p.o.) and nebracetam (100 mg/kg, p.o.). Cholinesterase inhibitors such as tetrahydroaminoacridine (1 and 10 mg/kg, p.o.), NIK-247 (10 and 18 mg/kg, p.o.) and physostigmine (0.32 mg/kg, i.p.) also suppressed the head-twitch response to mescaline. These results suggest that the direct or indirect cholinergic-activating effects of these drugs may be involved in inhibiting mescaline-induced head-twitches.
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Protective effect of Minaprine against the abnormal changes of 2-deoxyglucose uptake by rat hippocampal slices induced by hypoxia/hypoglycemia.
The Japanese Journal of Pharmacology, 1992Co-Authors: Kohtaroh Kodama, Shigenobu Shibata, Showa UekiAbstract:Effect of Minaprine on hypoxia or hypoxia/hypoglycemia (ischemia)-induced impairment of 2-deoxyglucose (2DG) uptake by rat hippocampal slices was evaluated. Since Minaprine was found to possess both a stimulating effect on acetylcholine release and a blocking effect on 5-HT2 receptors, the improving effect of Minaprine on impaired 2DG uptake was compared to the findings obtained with oxotremorine, ketanserin and pentobarbital. Hippocampal slices were exposed to 20-min ischemia, and then these slices were returned to oxygenated and glucose-containing buffer for 6 hr. Ischemia reduced 30 mM KCl-induced 2DG uptake by the hippocampus. Pretreatment with Minaprine, oxotremorine, pentobarbital and ketanserin attenuated the ischemia-induced decline of 2DG uptake. In addition, Minaprine, oxotremorine and pentobarbital relatively recovered the increase of 2DG uptake in the hippocampal slices under hypoxia for 45 min. The present results suggest that Minaprine exerts a neuroprotective action against ischemia-induced deficit of energy metabolism in vitro.
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protective effect of Minaprine against the abnormal changes of 2 deoxyglucose uptake by rat hippocampal slices induced by hypoxia hypoglycemia
Japanese Journal of Pharmacology, 1992Co-Authors: Kohtaroh Kodama, Shigenobu Shibata, Showa UekiAbstract:Effect of Minaprine on hypoxia or hypoxia/hypoglycemia (ischemia)-induced impairment of 2-deoxyglucose (2DG) uptake by rat hippocampal slices was evaluated. Since Minaprine was found to possess both a stimulating effect on acetylcholine release and a blocking effect on 5-HT2 receptors, the improving effect of Minaprine on impaired 2DG uptake was compared to the findings obtained with oxotremorine, ketanserin and pentobarbital. Hippocampal slices were exposed to 20-min ischemia, and then these slices were returned to oxygenated and glucose-containing buffer for 6 hr. Ischemia reduced 30 mM KCl-induced 2DG uptake by the hippocampus. Pretreatment with Minaprine, oxotremorine, pentobarbital and ketanserin attenuated the ischemia-induced decline of 2DG uptake. In addition, Minaprine, oxotremorine and pentobarbital relatively recovered the increase of 2DG uptake in the hippocampal slices under hypoxia for 45 min. The present results suggest that Minaprine exerts a neuroprotective action against ischemia-induced deficit of energy metabolism in vitro.
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Working and reference memory in rats in the three-panel runway task following dorsal hippocampal lesions.
The Japanese Journal of Pharmacology, 1992Co-Authors: Iwao Kitajima, Masuo Ohno, Tsuneyuki Yamamoto, Showa UekiAbstract:Using a three-panel runway task, the influence of dorsal hippocampal lesions on working and reference memory in rats was investigated. Despite 20 postoperative training sessions, rats with hippocampal lesions were unable to perform the working memory task. In the acquisition process of the reference memory task, however, there was no significant difference between hippocampal- and sham-lesioned rats. On the other hand, rats trained preoperatively with a working memory procedure, and then subjected to hippocampal lesions, showed more errors (pushes made on the two incorrect panels of the three panel-gates located at four choice points) than did sham-lesioned rats. The increase in working errors induced by hippocampal lesions was not reduced during 10 subsequent re-training sessions. Hippocampal lesions had no effect on retention of the reference memory performance. The increase in working errors in hippocampal-lesioned rats was significantly reduced by treatment with the cholinesterase inhibitor physostigmine at 0.1 mg/kg and the cholinergic activating drug Minaprine at 10 mg/kg. These findings suggest that lesions of the dorsal hippocampus selectively impair the ability to carry out the working memory task whether rats are trained preoperatively or postoperatively, and that the working memory loss in hippocampal-lesioned rats is mediated by lowering of the cholinergic function.
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Minaprine improves impairment of working memory induced by scopolamine and cerebral ischemia in rats
Psychopharmacology, 1990Co-Authors: Tsuneyuki Yamamoto, Shinichi Yatsugi, Masuo Ohno, Yoshiaki Furuya, Iwao Kitajima, Showa UekiAbstract:Using a repeated acquisition procedure in a three-panel runway apparatus, the effects of Minaprine on the impairment of working memory produced by scopolamine, ethylcholine aziridinium ion (AF64A) or cerebral ischemia were investigated in rats. Minaprine (3.2–32 mg/kg IP) as well as idebenone (10–100 mg/kg IP) and physostigmine (0.1–0.32 mg/kg IP) dose-dependently reduced the increase of errors (pushes made on the two incorrect panels located at each choice point) induced by 0.56 mg/kg IP scopolamine. Cerebral ischemia for 5 min caused a significant increase of errors in the runway task. Minaprine at 3.2 and 10 mg/kg administered IP immediately after blood recirculation and again 30 min before the runway test conducted 24 h after ischemia, significantly reduced increases in errors expected to occur after 5 min of ischemia. Physostigmine 0.1 mg/kg similarly attenuated the increase in errors in ischemic rats. However, Minaprine at doses up to 32 mg/kg IP failed to reduce the increase of errors induced by AF64A 2.5 nmol injected into the dorsal hippocampus. These findings suggest that Minaprine exerts an ameliorating effect on amnesia produced by scopolamine and cerebral ischemia, probably through mediation of its stimulant action on central cholinergic systems.
Susumu Otomo - One of the best experts on this subject based on the ideXlab platform.
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Involvement of protein kinase C activation in regulation of acetylcholine release from rat hippocampal slices by Minaprine.
Neurochemistry International, 1994Co-Authors: Shigeyuki Chaki, Makoto Muramatsu, Susumu OtomoAbstract:Abstract Involvement of protein kinase C (PKC) activation in the regulation of acetylcholine (ACh) release from rat hippocampal slices by Minaprine, [3(2-morpholinoethylamino)-4-methyl-6-phenylpyridazine] was investigated. Phorbol esters such as 4 β-phorbol 12,13-dibutylate (PDBu) and 12- o -tetradecanoylphorbol 13-acetate (TPA) enhanced high K + -evoked [ 3 H]ACh release from rat hippocampal slices. The enhancing effect of phorbol ester was attenuated by PKC inhibitors, staurosporine and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7). However, the inactive phorbol analogue, 4 α-phorbol 12,13-didecanoate (PDD) had no effect on [ 3 H]ACh release. Minaprine and 4-aminopyridine (4-AP) attenuated the inhibitory effect of 5-hydroxytryptamine (5-HT) on high K + -evoked [ 3 H]ACh release from rat hippocampal slices. The attenuating effect of Minaprine on the inhibition of [ 3 H]ACh release by 5-HT was prevented by staurosporine, while that of 4-AP was not influenced. Furthermore, PDBu blocked voltage-dependent, rapidly inactivating 42 K efflux from rat brain synaptosomes. These results suggest that Minaprine attenuates the inhibitory effect of 5-HT on ACh release via PKC activation in rat hippocampus, and that the blockade of the K + channel with PKC activation might be involved in the action of Minaprine.
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Cholinomimetic activity of Minaprine is related to the amelioration of delayed neuronal death in gerbils.
Physiology & Behavior, 1992Co-Authors: Yasuko Karasawa, Hiroaki Araki, Susumu OtomoAbstract:Abstract We attempted to determine if the cholinomimetic activity of the psychotropic drug Minaprine was related to the amelioration of the delayed neuronal death induced by cerebral ischemia in Mongolian gerbils. Minaprine improved the passive avoidance deficit induced by cerebral ischemia, and the histopathological ischemic neuronal changes in the hippocampal CA1 neurons were diminished. These effects were completely inhibited by treatment with the cholinergic blocker scopolamine. Rectal temperature fell about 1.5°C immediately after cerebral ischemia and hyperthermia occurred 30 and 60 min after recirculation. Minaprine had no effect on body temperature before or after ischemia. Physostigmine and tetrahydroaminoacridine (THA), drugs which stimulate the cholinergic system, improved passive avoidance deficits and prevented the delayed neuronal death. These effects of physostigmine and THA were completely inhibited by scopolamine. Pentobarbital and diazepam also improved the passive avoidance deficit and prevented the destruction of CA1 neurons. In contrast with Minaprine, these effects of pentobarbital and diazepam were not inhibited by scopolamine. As the protective effect of Minaprine against ischemia-induced delayed neuronal death is related to cholinomimetic activities, these events differ from those seen with pentobarbital and diazepam.
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blockade of voltage dependent 42k efflux from rat brain synaptosome by Minaprine and tetrahydroaminoacridine
Life Sciences, 1991Co-Authors: Shigeyuki Chaki, Makoto Muramatsu, Susumu OtomoAbstract:Abstract The effect of Minaprine (3-(2-morpholinoethylamino)- 4-methyl-6-phenylpyridazine) on the K + channels was studied by means of 42 K efflux from rat brain synaptosomes, comparing the effects of 4-aminopyridine and 9-amino-1,2,3,4-tetrahydroacridine (THA). 42 K efflux from rat brain synaptosomes was classified into five components: a resting component (R), a rapidly inactivating, voltage-dependent component (T), a slowly inactivating, voltage-dependent component (S) and a voltage-dependent, Ca 2+ -dependent component which is divided into a fast phase (C T ) and a slower phase (C S ). 4-Aminopyridine selectively inhibited 42 K efflux of component T. THA blocked both S and T components. The inhibitory effect of THA on the 42 K efflux of component S was quite pronounced compared with that of component T. Minaprine inhibited the 42 K efflux of components S and T but the inhibitory effect on component S was observed with a lower dose of Minaprine than that needed for the effect on component T. Minaprine had no effect on the Ca 2+ -dependent component while THA blocked component C T . 42 K efflux of the resting component was not changed by Minaprine, THA or 4- aminopyridine. These results suggest that Minaprine blocks Ca 2+ independent voltage-dependent K + channel is involved in the pharmacological actions of Minaprine.
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Biochemical and autoradiographic studies of specific [3H]Minaprine binding to rat brain slices
Neurochemistry International, 1991Co-Authors: Chika Usuki-ito, Shigeyuki Chaki, Makoto Muramatsu, Shigeru Okuyama, Susumu OtomoAbstract:Abstract The specific binding of Minaprine [3-(2-morpholino ethylamino)-4-methyl-6-phenyl pyridazine] to rat brain slices was examined. The specific binding of [3H]Minaprine was observed in brain sections mounted on a glass slide. The binding was saturable and reversible. Scatchard analysis demonstrated that [3H]Minaprine had a high affinity specific binding site in the brain. The dissociation constant (Kd) and the maximum number of binding sites was 32.1 nM and 213.0 fmol/section, respectively. In a displacement experiment, the binding of [3H]Minaprine to the sections was blocked by Minaprine and voltage-dependent K+ channel blockers, 4-aminopyridine and dendrotoxin. In an autoradiographic study, the binding site of [3H]Minaprine was widely distributed in the brain with higher specific binding in the cortical area (cingulate, frontal, sensory and occipital cortex), hippocampus, striatum and molecular layer of the cerebellum. These results suggest that Minaprine has a specific binding site which is high affinity, saturable and reversible, in the brain, and that the site is related to a voltage dependent K+ channel.
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Protective effects of Minaprine in infarction produced by occluding middle cerebral artery in stroke-prone spontaneously hypertensive rats.
General Pharmacology: The Vascular System, 1991Co-Authors: Shigeru Okuyama, Kazuaki Kawashima, Susumu Otomo, Yasuko Karasawa, Hiroaki Araki, Hiroko Shimamura-harada, Masaaki Kimura, Hironaka AiharaAbstract:Abstract 1. 1. We examined the effects of Minaprine on cerebral infarction produced by occluding of unilateral middle cerebral artery (MCA) above the rhinal fissure in stroke-prone spontaneously hypertensive rats (SHRSP). 2. 2. Oral administration of Minaprine (60 mg/kg/day) and vehicle were started 30 min after the occlusion of MCA, and continued for 6 days. 3. 3. The brain was dissected out and 36 coronal multiple sections of the whole brain were histologically prepared to determine the location and extension of infarction. 4. 4. The infarcted area produced by the occlusion of MCA was limited to the cerebral cortex. 5. 5. Body weight of the Minaprine-treated rats gradually decreased within 4 days after the occlusion of MCA and thereafter increased, whereas in the vehicle-treated rats, there was a gradual decrease during the experimental period. 6. 6. Size of the infarcted area was serially measured, in each section, using a microcomputer imaging device. In all animals with an occluded MCA, there was a typical pattern of ischemic damage. 7. 7. Post-treatment of MCA occluded SHRSP with Minaprine resulted in reduction in infarct size, as compared to findings in the vehicle-treated controls. 8. 8. The pharmacological and histopathological effects of Minaprine on the progress of cerebral infarction produced by the occlusion of MCA in SHRSP are discussed.
Stefano Puglisi-allegra - One of the best experts on this subject based on the ideXlab platform.
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A comparison of the behavioral effects of Minaprine, amphetamine and stress
Psychopharmacology, 1995Co-Authors: Simona Cabib, Alessandro Zocchi, Stefano Puglisi-allegraAbstract:Different types of clinically effective antidepressants prevent the behavioral effects of experimental stress, and some of these treatments affect mesolimbic dopamine (DA) functioning. Animal studies have demonstrated that repeated psychostimulant administration and repeated or chronic stressful experiences also affect mesolimbic DA functioning. These results could suggest homologies among stress, psychostimulants and antidepressants. The present experiments show that either repeated stress (120min restraint daily for 10 consecutive days) or subchronic treatment with the antidepressant Minaprine (5 mg/kg daily for 10 consecutive days) significantly reduced the inhibitory effect of 120 min of restraint on climbing, a behavioral response dependent on mesolimbic DA functioning. However, the antidepressant did not induce the altered sensitivity of presynaptic DA receptors promoted by repeated stress. Chronic stressful experience (13 days of food restriction) and repeated amphetamine (2.5 mg/kg daily for 10 consecutive days) were as effective as subchronic Minaprine in reducing immobility in the Porsolt's swimming test. However, whilst both stress and amphetamine enhanced struggling, Minaprine promoted swimming. Finally, chronically stressed mice and mice pretreated with amphetamine showed enhanced sensitivity to amphetamine-induced locomotion, whilst this effect was absent in animals pretreated with the antidepressant. These results indicate that although chronic and repeated stress as well as amphetamine have some antidepressant-like behavioral effects, their mode of action could be different from that of clinically active substances.
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Effects of subchronic Minaprine on dopamine release in the ventral striatum and on immobility in the forced swimming test.
Neuroscience Letters, 1994Co-Authors: Assunta Imperato, Maria Carmen Obinu, Simona Cabib, Vincenzo Cestari, Stefano Puglisi-allegraAbstract:Subchronic (5 mg/kg daily for 9 consecutive days) but not acute Minaprine treatment enhanced in vivo dopamine release in the limbic part of the striatum of rats as revealed by intracerebral microdialysis. Moreover, the same subchronic treatment with Minaprine reduced immobility in the forced swimming test. The anti-immobility effect of Minaprine was not evident after a single injection of the antidepressant. Finally, the subchronic treatment with Minaprine was devoid of effects in an activity test. These results suggest that enhanced dopaminergic transmission may contribute to the pharmacological and clinical profile of this drug.
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Post-training Minaprine enhances memory storage in mice: involvement of D_1 and D_2 dopamine receptors
Psychopharmacology, 1994Co-Authors: Stefano Puglisi-allegra, Simona Cabib, Vincenzo Cestari, Claudio CastellanoAbstract:Post-training administration of Minaprine (2.5, 5 and 10 mg/kg) dose-dependently improved retention of an inhibitory avoidance response in mice. Animals receiving nine daily injections of 5 mg/kg and administered a challenge dose post-training showed an improvement in memory consolidation similar to that produced by acute injection of 10 mg/kg. The effects on retention performance induced by the drug appear to be due to an effect on memory consolidation. They were observed when drugs were given at short, but not long, periods of time after training, i.e. when the memory trace was susceptible to modulation. Moreover, these effects are not to be ascribed to an aversive or a rewarding or non-specific action of the drugs on retention performance, as the latencies during the retention test of those mice that had not received a footshock during training were not affected by post-training drug administration. The effects of an acutely injected dose (10 mg/kg) of Minaprine as well as those of a challenge dose (5 mg/kg) of the drug administered to repeatedly treated animals were reversed by pretreatment with either selective D_1 or D_2 dopamine receptor antagonists SCH 23390 and (-)-sulpiride administered at per se non-effective doses (0.025 and 6 mg/kg, respectively), thus suggesting that D_1 and D_2 receptor types are similarly involved in the effects of Minaprine on memory consolidation. These results show that Minaprine improves memory consolidation and that repeated drug administration leads to potentiation of this effect. Moreover, the effects of Minaprine on memory consolidation are related to its dopaminergic action.
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Post-training Minaprine enhances memory storage in mice: involvement of D1 and D2 dopamine receptors
Psychopharmacology, 1994Co-Authors: Stefano Puglisi-allegra, Simona Cabib, Vincenzo Cestari, Claudio CastellanoAbstract:Post-training administration of Minaprine (2.5, 5 and 10 mg/kg) dose-dependently improved retention of an inhibitory avoidance response in mice. Animals receiving nine daily injections of 5 mg/kg and administered a challenge dose post-training showed an improvement in memory consolidation similar to that produced by acute injection of 10 mg/kg. The effects on retention performance induced by the drug appear to be due to an effect on memory consolidation. They were observed when drugs were given at short, but not long, periods of time after training, i.e. when the memory trace was susceptible to modulation. Moreover, these effects are not to be ascribed to an aversive or a rewarding or non-specific action of the drugs on retention performance, as the latencies during the retention test of those mice that had not received a footshock during training were not affected by post-training drug administration. The effects of an acutely injected dose (10 mg/kg) of Minaprine as well as those of a challenge dose (5 mg/kg) of the drug administered to repeatedly treated animals were reversed by pretreatment with either selective D1 or D2 dopamine receptor antagonists SCH 23390 and (-)-sulpiride administered at per se non-effective doses (0.025 and 6 mg/kg, respectively), thus suggesting that D1 and D2 receptor types are similarly involved in the effects of Minaprine on memory consolidation. These results show that Minaprine improves memory consolidation and that repeated drug administration leads to potentiation of this effect. Moreover, the effects of Minaprine on memory consolidation are related to its dopaminergic action.
Shigeyuki Chaki - One of the best experts on this subject based on the ideXlab platform.
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Involvement of protein kinase C activation in regulation of acetylcholine release from rat hippocampal slices by Minaprine.
Neurochemistry International, 1994Co-Authors: Shigeyuki Chaki, Makoto Muramatsu, Susumu OtomoAbstract:Abstract Involvement of protein kinase C (PKC) activation in the regulation of acetylcholine (ACh) release from rat hippocampal slices by Minaprine, [3(2-morpholinoethylamino)-4-methyl-6-phenylpyridazine] was investigated. Phorbol esters such as 4 β-phorbol 12,13-dibutylate (PDBu) and 12- o -tetradecanoylphorbol 13-acetate (TPA) enhanced high K + -evoked [ 3 H]ACh release from rat hippocampal slices. The enhancing effect of phorbol ester was attenuated by PKC inhibitors, staurosporine and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7). However, the inactive phorbol analogue, 4 α-phorbol 12,13-didecanoate (PDD) had no effect on [ 3 H]ACh release. Minaprine and 4-aminopyridine (4-AP) attenuated the inhibitory effect of 5-hydroxytryptamine (5-HT) on high K + -evoked [ 3 H]ACh release from rat hippocampal slices. The attenuating effect of Minaprine on the inhibition of [ 3 H]ACh release by 5-HT was prevented by staurosporine, while that of 4-AP was not influenced. Furthermore, PDBu blocked voltage-dependent, rapidly inactivating 42 K efflux from rat brain synaptosomes. These results suggest that Minaprine attenuates the inhibitory effect of 5-HT on ACh release via PKC activation in rat hippocampus, and that the blockade of the K + channel with PKC activation might be involved in the action of Minaprine.
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blockade of voltage dependent 42k efflux from rat brain synaptosome by Minaprine and tetrahydroaminoacridine
Life Sciences, 1991Co-Authors: Shigeyuki Chaki, Makoto Muramatsu, Susumu OtomoAbstract:Abstract The effect of Minaprine (3-(2-morpholinoethylamino)- 4-methyl-6-phenylpyridazine) on the K + channels was studied by means of 42 K efflux from rat brain synaptosomes, comparing the effects of 4-aminopyridine and 9-amino-1,2,3,4-tetrahydroacridine (THA). 42 K efflux from rat brain synaptosomes was classified into five components: a resting component (R), a rapidly inactivating, voltage-dependent component (T), a slowly inactivating, voltage-dependent component (S) and a voltage-dependent, Ca 2+ -dependent component which is divided into a fast phase (C T ) and a slower phase (C S ). 4-Aminopyridine selectively inhibited 42 K efflux of component T. THA blocked both S and T components. The inhibitory effect of THA on the 42 K efflux of component S was quite pronounced compared with that of component T. Minaprine inhibited the 42 K efflux of components S and T but the inhibitory effect on component S was observed with a lower dose of Minaprine than that needed for the effect on component T. Minaprine had no effect on the Ca 2+ -dependent component while THA blocked component C T . 42 K efflux of the resting component was not changed by Minaprine, THA or 4- aminopyridine. These results suggest that Minaprine blocks Ca 2+ independent voltage-dependent K + channel is involved in the pharmacological actions of Minaprine.
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Biochemical and autoradiographic studies of specific [3H]Minaprine binding to rat brain slices
Neurochemistry International, 1991Co-Authors: Chika Usuki-ito, Shigeyuki Chaki, Makoto Muramatsu, Shigeru Okuyama, Susumu OtomoAbstract:Abstract The specific binding of Minaprine [3-(2-morpholino ethylamino)-4-methyl-6-phenyl pyridazine] to rat brain slices was examined. The specific binding of [3H]Minaprine was observed in brain sections mounted on a glass slide. The binding was saturable and reversible. Scatchard analysis demonstrated that [3H]Minaprine had a high affinity specific binding site in the brain. The dissociation constant (Kd) and the maximum number of binding sites was 32.1 nM and 213.0 fmol/section, respectively. In a displacement experiment, the binding of [3H]Minaprine to the sections was blocked by Minaprine and voltage-dependent K+ channel blockers, 4-aminopyridine and dendrotoxin. In an autoradiographic study, the binding site of [3H]Minaprine was widely distributed in the brain with higher specific binding in the cortical area (cingulate, frontal, sensory and occipital cortex), hippocampus, striatum and molecular layer of the cerebellum. These results suggest that Minaprine has a specific binding site which is high affinity, saturable and reversible, in the brain, and that the site is related to a voltage dependent K+ channel.
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Differentiation of the active site of Minaprine from that of phencyclidine in rat hippocampus.
Research communications in chemical pathology and pharmacology, 1990Co-Authors: Shigeyuki Chaki, Makoto Muramatsu, Chika Usuki-ito, Susumu OtomoAbstract:The active site of Minaprine (3-(2-morpholinoethylamino)-4-methyl-6-phenylpyridazine) was studied by means of receptor binding and its effect on acetylcholine (ACh) release in rat hippocampus. [3H]Minaprine binding to the hippocampal membrane was inhibited by Minaprine, 4-aminopyridine (4-AP) and phencyclidine (PCP) dose-dependently, whereas it was not inhibited by L-glutamate (L-Glu), N-methyl-D-aspartate (NMDA), 2-amino-5-phosphonovalerate (APV), 3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)3-PPP) or ketamine. [3H]PCP binding was inhibited by PCP and APV in an extensively washed hippocampal membrane. Minaprine, however, failed to inhibit the [3H]PCP binding. [3H]3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) binding was inhibited by L-Glu but not by Minaprine. NMDA-evoked [3H]ACh release from the rat hippocampal slices was effectively inhibited by PCP. However, Minaprine had no effect on the NMDA-evoked [3H]ACh release. Similar results were obtained from the study of [3H]ACh release in the striatum. These results suggest that Minaprine exerts its action via the voltage-dependent K+ channel but not via the NMDA receptor-channel complex or sigma receptor.
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Attenuation of serotonin-suppressed [3H]acetylcholine release by tetrahydroaminoacridine and dendrotoxin: interaction with Minaprine binding site.
Research communications in chemical pathology and pharmacology, 1990Co-Authors: Makoto Muramatsu, Shigeyuki Chaki, Chika Usuki-ito, Susumu OtomoAbstract:5-Hydroxytryptamine (5-HT) inhibited K(+)-induced [3H]acetylcholine ([3H]ACh) release from rat hippocampal slices dose-dependently. Minaprine [3-(2-morpholino-ethylamino)-4-methyl-6-phenylpyridazine] and 9-amino-1,2,3,4-tetrahydroacridine (THA) attenuated the inhibition of [3H]ACh release by 5-HT. A neurotoxin isolated from the venom of Dendroaspis snake, dendrotoxin (DTX), also attenuated the 5-HT inhibited [3H]ACh release from hippocampal slices dose-dependently at doses of more than 3 x 10(-7) g/ml (about 42 nM). Specific binding of [3H]Minaprine to hippocampal membrane was dose-dependently inhibited by THA and DTX. The IC50 of THA and DTX for the [3H]Minaprine binding were about 32 and 0.7 mu M, respectively. Scatchard plot analyses showed that the inhibitory effects of THA and DTX were noncompetitive for [3H]Minaprine binding. THA and DTX inhibited [3H]ketanserin binding with IC50 of 28.8 and 26.2 mu M, respectively. These results suggest that THA and DTX attenuate the 5-HT-inhibited [3H]ACh release by blocking a voltage-dependent K+ current, and that they interact with the binding site of Minaprine in the hippcampus.
Simona Cabib - One of the best experts on this subject based on the ideXlab platform.
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A comparison of the behavioral effects of Minaprine, amphetamine and stress
Psychopharmacology, 1995Co-Authors: Simona Cabib, Alessandro Zocchi, Stefano Puglisi-allegraAbstract:Different types of clinically effective antidepressants prevent the behavioral effects of experimental stress, and some of these treatments affect mesolimbic dopamine (DA) functioning. Animal studies have demonstrated that repeated psychostimulant administration and repeated or chronic stressful experiences also affect mesolimbic DA functioning. These results could suggest homologies among stress, psychostimulants and antidepressants. The present experiments show that either repeated stress (120min restraint daily for 10 consecutive days) or subchronic treatment with the antidepressant Minaprine (5 mg/kg daily for 10 consecutive days) significantly reduced the inhibitory effect of 120 min of restraint on climbing, a behavioral response dependent on mesolimbic DA functioning. However, the antidepressant did not induce the altered sensitivity of presynaptic DA receptors promoted by repeated stress. Chronic stressful experience (13 days of food restriction) and repeated amphetamine (2.5 mg/kg daily for 10 consecutive days) were as effective as subchronic Minaprine in reducing immobility in the Porsolt's swimming test. However, whilst both stress and amphetamine enhanced struggling, Minaprine promoted swimming. Finally, chronically stressed mice and mice pretreated with amphetamine showed enhanced sensitivity to amphetamine-induced locomotion, whilst this effect was absent in animals pretreated with the antidepressant. These results indicate that although chronic and repeated stress as well as amphetamine have some antidepressant-like behavioral effects, their mode of action could be different from that of clinically active substances.
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Effects of subchronic Minaprine on dopamine release in the ventral striatum and on immobility in the forced swimming test.
Neuroscience Letters, 1994Co-Authors: Assunta Imperato, Maria Carmen Obinu, Simona Cabib, Vincenzo Cestari, Stefano Puglisi-allegraAbstract:Subchronic (5 mg/kg daily for 9 consecutive days) but not acute Minaprine treatment enhanced in vivo dopamine release in the limbic part of the striatum of rats as revealed by intracerebral microdialysis. Moreover, the same subchronic treatment with Minaprine reduced immobility in the forced swimming test. The anti-immobility effect of Minaprine was not evident after a single injection of the antidepressant. Finally, the subchronic treatment with Minaprine was devoid of effects in an activity test. These results suggest that enhanced dopaminergic transmission may contribute to the pharmacological and clinical profile of this drug.
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Post-training Minaprine enhances memory storage in mice: involvement of D_1 and D_2 dopamine receptors
Psychopharmacology, 1994Co-Authors: Stefano Puglisi-allegra, Simona Cabib, Vincenzo Cestari, Claudio CastellanoAbstract:Post-training administration of Minaprine (2.5, 5 and 10 mg/kg) dose-dependently improved retention of an inhibitory avoidance response in mice. Animals receiving nine daily injections of 5 mg/kg and administered a challenge dose post-training showed an improvement in memory consolidation similar to that produced by acute injection of 10 mg/kg. The effects on retention performance induced by the drug appear to be due to an effect on memory consolidation. They were observed when drugs were given at short, but not long, periods of time after training, i.e. when the memory trace was susceptible to modulation. Moreover, these effects are not to be ascribed to an aversive or a rewarding or non-specific action of the drugs on retention performance, as the latencies during the retention test of those mice that had not received a footshock during training were not affected by post-training drug administration. The effects of an acutely injected dose (10 mg/kg) of Minaprine as well as those of a challenge dose (5 mg/kg) of the drug administered to repeatedly treated animals were reversed by pretreatment with either selective D_1 or D_2 dopamine receptor antagonists SCH 23390 and (-)-sulpiride administered at per se non-effective doses (0.025 and 6 mg/kg, respectively), thus suggesting that D_1 and D_2 receptor types are similarly involved in the effects of Minaprine on memory consolidation. These results show that Minaprine improves memory consolidation and that repeated drug administration leads to potentiation of this effect. Moreover, the effects of Minaprine on memory consolidation are related to its dopaminergic action.
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Post-training Minaprine enhances memory storage in mice: involvement of D1 and D2 dopamine receptors
Psychopharmacology, 1994Co-Authors: Stefano Puglisi-allegra, Simona Cabib, Vincenzo Cestari, Claudio CastellanoAbstract:Post-training administration of Minaprine (2.5, 5 and 10 mg/kg) dose-dependently improved retention of an inhibitory avoidance response in mice. Animals receiving nine daily injections of 5 mg/kg and administered a challenge dose post-training showed an improvement in memory consolidation similar to that produced by acute injection of 10 mg/kg. The effects on retention performance induced by the drug appear to be due to an effect on memory consolidation. They were observed when drugs were given at short, but not long, periods of time after training, i.e. when the memory trace was susceptible to modulation. Moreover, these effects are not to be ascribed to an aversive or a rewarding or non-specific action of the drugs on retention performance, as the latencies during the retention test of those mice that had not received a footshock during training were not affected by post-training drug administration. The effects of an acutely injected dose (10 mg/kg) of Minaprine as well as those of a challenge dose (5 mg/kg) of the drug administered to repeatedly treated animals were reversed by pretreatment with either selective D1 or D2 dopamine receptor antagonists SCH 23390 and (-)-sulpiride administered at per se non-effective doses (0.025 and 6 mg/kg, respectively), thus suggesting that D1 and D2 receptor types are similarly involved in the effects of Minaprine on memory consolidation. These results show that Minaprine improves memory consolidation and that repeated drug administration leads to potentiation of this effect. Moreover, the effects of Minaprine on memory consolidation are related to its dopaminergic action.