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K Yamatsu

Publications and source records attributed to K Yamatsu.

At least 37 records · Page 2Linked to original sources
PubMed1990

Synthesis and structure-activity relationships of [MeTyr1, MeArg7]-dynorphin A(1-8)-OH analogues with substitution at position 8.

A series of [MeTyr1, MeArg7]-Dynorphin A (Dyn)(1-8)-OH analogues, modified at position 8 with various amino acids, is described. Their biological activities were determined in the three bioassays [guinea pig ileum (GPI), mouse vas deferens (MVD), and rabbit vas deferens (RVD)] and in the mouse tail-pinch test after subcutaneous administration. None of the analogues tested displayed more potent kappa-opioid activity in the RVD than [MeTyr1, MeArg7, D-Leu8]-Dyn(1-8)-NHEt (1), which is a potent analgesic peptide with similar opioid receptor selectivity to that of Dyn. However, [MeTyr1, MeArg7, Melle8]-Dyn(1-8)-OH (11) showed about a twofold more potent analgesic effect than 1. Based on the obtained results it is conceivable that in the case of Dyn(1-8)-OH analogues both a lipophilic L-amino acid in position 8 and an unchanged 7-8 amide bond are essential to maintain potent kappa-opioid activity.

Animals↗
PubMed1990

Analgesia produced by E-2078, a systemically active dynorphin analog, in mice.

E-2078 is a very stable dynorphin analog that has the same affinity and selectivity for opioid receptors as dynorphin-A by in vitro bioassay. In the present study, we have characterized the receptor selectivity of E-2078 in mu-, delta- and kappa-representative binding assays, and have evaluated the analgesic effect of systemically administered E-2078 by the tail pinch, tail flick and formalin tests in mice. E-2078 possessed a higher affinity for kappa-receptors than for mu- or delta-receptors in the receptor-binding assay. Dose-related, long-lasting analgesia was produced by s.c. injection of E-2078, and its peak effect was observed 2 hr after s.c. administration in all the analgesic tests. This analgesic effect was produced at doses that did not affect rotarod latency. Post-treatment with naloxone dose-dependently reversed the analgesic effects of both E-2078 and morphine, but E-2078-induced analgesia was relatively resistant to naloxone antagonism. Pre-treatment with the kappa-antagonist, nor-binaltorphimine, antagonized the analgesic effect of E-2078 but had little effect on the analgesic action of morphine. These data indicate that E-2078 is a systemically active analgesic and suggest that the activation of kappa-opioid receptors contributes to analgesia.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1990

Protective effect of the novel anti-ischemic agent 2-(4-(p-fluorobenzoyl)-piperidin-1-yl)-2'-acetonaphthone hydrochloride against ischemia-induced impairment of the passive avoidance response in gerbils.

E2001 (2-(4-(p-fluorobenzoyl)-piperidin-1-yl)-2'-acetonaphthone hydrochloride, CAS 107025-80-9) is a novel anti-ischemic agent, which is reported to protect against delayed neuronal death in the CA1 subfield of the hippocampus. The effect of E2001 on ischemia-induced impairment of the passive avoidance response in gerbils was studied. The passive avoidance response was not disturbed by transient cerebral ischemia of 3 min duration, but was impaired by 5-min ischemia. E2001 at oral doses of 3 and 10 mg/kg significantly improved the impaired passive avoidance response induced by 5-min cerebral ischemia. It is speculated that the improvement by E2001 may be partly due to the inhibition of extracellular glutamate accumulation, and the suppression of lipid peroxides formation during cerebral ischemia.

Animals↗
PubMed1989

Extracellular accumulation of glutamate in the hippocampus induced by ischemia is not calcium dependent--in vitro and in vivo evidence.

Calcium dependency of ischemia-induced increase in extracellular glutamate in the hippocampus was studied in vitro and in vivo. Perfusion of a low pO2 medium without glucose (in vitro ischemia) induced an increase in extracellular glutamate in rat hippocampal slices. This increase did not depend on Ca2+, which is in contrast with the observation that about 40% of membrane depolarization (50 mM KCl)-evoked release was Ca2+-dependent. In vivo cerebral ischemia of 5 min duration in gerbils also caused Ca2+-independent increase in extracellular glutamate in the hippocampus. The data suggest that the increase in extracellular glutamate induced by ischemia is not due to the enhanced release of neurotransmitter glutamate.

Animals↗
PubMed1987

Effects of physostigmine on AF64A-induced impairment of learning acquisition in rats.

Ethylcholine aziridinium ion (AF64A), a putative cholinotoxin, was administered into the cerebroventricles of rats, and the effects on learning behaviors were observed. AF64A caused the impairment of learning acquisition in both passive and active avoidance responses. Physostigmine, a cholinesterase inhibitor, antagonized these changes at the doses of 0.03 to 0.1 mg/kg. Our behavioral study may indicate that the central cholinergic system might play a role in AF64A-induced impairment.

Animals↗
PubMed1983

Sites of analgesic action of dynorphin.

Analgesic effects of dynorphin and dynorphin-(1-13) injected into various regions of the CNS of rats were investigated using the tail pinch method. Dynorphin and dynorphin-(1-13) produced a dose-dependent analgesic effect when injected into the third ventricle (3rd vent.) or the nuclei reticularis gigantocellularis and paragigantocellularis (NRGC-NRPG) and the analgesic activity of dynorphin was 3 to 5 times more potent than that of dynorphin-(1-13). These peptides in higher doses elicited transient "barrel-rolling" and rigidity in behavior. On the other hand, when injected intrathecally, dynorphin exerted an analgesia accompanied by paralysis of hindlimbs which were long lasting. But its analgesic activity was less effective as compared with the 3rd vent. and NRGC-NRPG injections.

Analgesia↗
PubMed1983

[Pharmacological studies of dl-2[3-(2'-chlorophenoxy)phenyl]propionic acid. I. Analgesic and antipyretic effects].

Analgesic and antipyretic effects of dl-2[3-(2'-chlorophenoxy)phenyl] propionic acid (CPP) were studied in mice, rats and guinea-pigs. CPP produced a dose dependent inhibition of acetic acid-induced writhing syndrome. Its ED50 values 1 and 3 hr after oral administration were 47 and 31 mg/kg, respectively. CPP had a potent analgesic effect on bradykinin-induced nociceptive response in rats, and its ED50 value was 15 mg/kg 2 hr after oral administration. The analgesic activity of CPP in these experiments was less potent than that of indomethacin, but it was approximately equivalent to ibuprofen and 10 to 20 times as potent as aspirin. CPP had no analgesic effect on both the tail pinch and hot plate tests in mice, while CPP potentiated the analgesic effect of codeine on these tests. CPP had no effect on the nociceptive response induced by intradermal injection of bradykinin and/or EDTA in guinea-pigs. On the other hand, when CPP was given orally in a dose range of 1.25 to 5 mg/kg, it produced an antipyretic effect on yeast-induced fever in rats. The antipyretic activity of CPP was equivalent to ibuprofen and 10 to 15 times as potent as aspirin.

Analgesics↗
PubMed1983

[Pharmacological studies of d1-2-[3-(2'-chlorophenoxy)phenyl]propionic acid. (2) Sites and mechanisms of analgesic and antipyretic effects].

Effects of d1-2-[3-(2'-chlorophenoxy)phenyl]propionic acid (CPP) on the nociceptive response induced by injection of bradykinin (BK) into rabbit femoral artery were studied. When drugs were administered intravenously, the analgesic activity of morphine was 2 to 10 times more potent than that of CPP; but when it was injected into the femoral artery, CPP was approximately 5 times more potent than morphine. Intraventricular injection of a small dose of 10 micrograms/head morphine produced a prominent analgesic activity, while even a large dose of 500 micrograms/head CPP had little effect. Prostaglandin E1 (PGE1) alone in a dose range of 0.1 to 1 microgram i.a. produced no nociceptive response, but an intra-arterial pre-injection of PGE1 enhanced BK-induced nociceptive response. Morphine suppressed the BK-response pretreated with PGE1, but CPP as well as indomethacin had little effect. These results suggest that CPP suppresses BK-induced nociceptive response at the periphery, probably at the paravascular "pain receptor", and the analgesic effect of CPP may be due to inhibition of endogenous PG synthesis. On the other hand, CPP in a dose range of 2.5 to 20 mg/kg, i.v. produced antipyretic effects on the fever induced by typhoid vaccine. Intraventricular injection of 500 micrograms/head CPP produced a slight antipyretic effect. CPP had no effect on PGE1 -induced fever. These results suggest that CPP produces the antipyretic effect acting on the central nervous system, probably due to inhibition of endogenous PG synthesis.

Alprostadil↗
PubMed1982

High performance liquid chromatography (HPLC) determination of endogenous serotonin released from aggregating platelets.

High performance liquid chromatography with electrochemical detection was developed for the determination of serotonin (5-hydroxytryptamine) in rabbit platelet and plasma. A peak from tissue extract (peak a) was identified as serotonin based on retention time on the chromatogram, using a potential that gave limiting current on both a current-potential curve and gas chromatography-mass spectrum, as compared with that of authentic serotonin. For the assay of serotonin, 5-hydroxy-N-methyltryptamine was used as an internal standard and the extraction recovery of the serotonin added to the platelet-rich plasma was almost total. Furthermore, using this highly sensitive method, it has been demonstrated that the release of endogenous serotonin from rabbit platelets occurs during collagen-induced platelet aggregation but not during adenosine diphosphate-induced platelet aggregation. The procedures described should prove to be simple and useful for pharmacological and physiological investigations on the relationship between platelet aggregation and release reaction.

Animals↗
PubMed1981

[Combined effect of flunitrazepam on activities of anesthetics and analgesics in mice and rats (author's transl)].

Flunitrazepam in a dose range of 0.01 to 1 mg/kg i.v. produced dose dependent sedation and muscle relaxation, while even 1 mg/kg of flunitrazepam had no anesthetic effect (loss of righting reflex). Flunitrazepam in a dose over 0.01 mg/kg prolonged anesthesia induced by pentobarbital, thiopental and ketamine in mice and rats and combinations of non-effective doses of these anesthetics with flunitrazepam induced anesthesia in mice. Furthermore, flunitrazepam enhanced gaseous anesthesia in mice and rats. Flunitrazepam alone was slightly effective in prevention of acetic acid writhing in mice and the drug enhanced the anti-writhing effects of morphine, pentazocine and thalamonal. Flunitrazepam alone had little analgesic effect on the hot plate test in mice, while it did enhance the effect of morphine. The analgesic effects of morphine and pentazocine on the tail pinch test in rats were potentiated with 0.1 and 1 mg/kg of flunitrazepam. Flunitrazepam had no effect on bradykinin-induced nociceptive response in rats, while 1 mg/kg of the drug enhanced morphine analgesia in this test. Combined effect of flunitrazepam on activities of anesthetics and analgesics may contribute to the clinical effect of this drug in cases of preanesthetic medication.

Analgesics↗
PubMed1981

Effects of azelastine hydrochloride, a novel anti-allergic drug, on the central nervous system.

The effects of 4-(p-chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1-(2H)-phthalazinone hydrochloride (azelastine hydrochloride), a new anti-allergic drug, on the central nervous system were studied in mice, rats and rabbits in comparison to clemastine, chlorpheniramine and diphenhydramine. In mice, azelastine showed a definite central action with the same dose range (10--40 mg/kg p.o.) as the reference drugs. However, the central action profile of azelastine was considerably different from those of the reference antihistaminics. Clemastine and diphenhydramine produced potent anti-tremorine and anti-pilocarpine activities, while azelastine was less active than the two drugs. Chlorpheniramine and diphenhydramine produced a marked anti-reserpine activity and a marked potentiation of the caffeine-induced hypermotility, while clemastine had little effect in this animal model; on the contrary, 40 mg/kg of azelastine suppressed the caffeine-induced hypermotility. In rats, a high dose of 100 mg/kg azelastine produced a slight suppression of the paradoxical sleep. But the drug affected neither the rectal temperature nor the conditioned avoidance response at oral doses up to 100 mg/kg. In unanesthetized and restrained rabbits, azelastine in a dose of 0.5 to 8 mg/kg i.v. showed no significant change in the spontaneous EEG activity and in the susceptibility of the ascending reticular activating system, whereas an i.v. dose of 2 mg/kg clemastine produced a marked high voltage and slow wave pattern in EEG activity and suppressed the reticular activating system.

Aggression↗
PubMed1981

[Effects of 4'ethyl-2-methyl-3-piperidinopropiophenone on experimental rigidity and spinal cord activities (author's transl)].

Effects of 4'ethyl-2-methyl-3-piperidonopropiophenone hydrochloride (EMPP) on experimental rigidities in rats and spinal cord activities in cats were studied. EMPP in a dose range of 1.25 approximately 10 mg/kg i.v. reduced EMG spikes of the intercollicular decerebrate rigidity and anemic decerebrate rigidity in rats. In alpha-chloralose anesthetized cats, EMPP in a dose range of 2.5 approximately 10 mg/kg i.v. caused a dose-related inhibition of the flexor reflex without any effect on the patellar reflex. In spinal cats, 2.5 approximately 10 mg/kg of EMPP caused a dose-related inhibition of the flexor reflex but the potency was less than that in anesthetized cats. Oral administration of EMPP 100 approximately 200 mg/kg produced a selective inhibition of the flexor reflex and the effect was twice as potent as tolperisone and chlormezanone. On the other hand, EMPP at 2.5 approximately 10 mg/kg i.v. which had little effect on the patellar reflex inhibited both monosynaptic and polysynaptic reflex potentials recorded from the ventral root to the same extent and also depressed dorsal root reflex potential recorded from the dorsal root in spinal cats. EMPP reduced the frequency of spontaneous gamma-motoneurone discharges in spinal cats, but had no appreciable effect on GIa discharges from muscle spindle of the triceps surae muscle. These results indicate that EMPP reduces alpha- and gamma-efferent activities and that EMPP exerts a marked inhibitory effect on spinal cord activities acting on the spinal cord and supraspinal structures.

Action Potentials↗
PubMed1976

[Pharmacological studies on degeneration and regeneration of peripheral nerves. (1) Effects of methylcobalamin and cobamide on EMG patterns and loss of muscle weight in rats with crushed sciatic nerve].

Experiments were performed to investigate the effects of Vitamin B12, i.e., methylcobalamin and cobamide, on the neural degeneration and regeneration. Male Wistar rats (140 to 150 g) under conditions of experimental unilateral sciatic nerve crushing were treated consecutively with methylcobalamin (50 and 500 mug/kg/day i.p.), cobamide (50 and 500 mug/kg/day i.p.) or saline. EMG recordings were periodically carried out and rats of each group were sacrificed to determine the weight-loss of denervated muscles 1, 2, 3 and 4 weeks after crush. Neither methylcobalamin nor cobamide exerted any significant effect on body-weight gain of the nerve-crushed rats with a daily injection of 50 and 500 mug/kg i.p.. The EMG pattern of the denervated biceps femoris muscle showed a total lack of fibrillation for 2 days after the nerve-crush. Thereafter, the fibrillation appeared and continued for 10 to 14 days until the nerve had regenerated, as evidenced by the appearance of a complex NMU voltage. The occurrence of fibrillation voltage was slightly delayed in methylcobalamin group (500 mug/kg/day) as compared with the saline control group. The re-appearance of normal NMU voltage was more rapid in the methylcobalamin 500 mug/kg group than in controls and other experimental groups. Neither methylcobalamin nor cobamide had any significant effect on the weight-loss of the gastrocnemius and tibialis anterior muscles following crush of the sciatic nerve. However, a daily injection of 500 mug/kg of methylcobalamin produced a significant increase in the weight of the soleus muscle which recovered to the extent of being the same weight of the contralateral 4 weeks after the nerve-crush. These results suggest that methylcobalamin may have an inhibitory effect on Wallerian degeneration and also a facilitatory effect on the neural regeneration of the crushed sciatic nerve of rats.

Animals↗
PubMed1976

[Pharmacological studies on degeneration and regeneration of the peripheral nerves. (2) Effects of methylcobalamin on mitosis of Schwann cells and incorporation of labeled amino acid into protein fractions of crushed sciatic nerve in rats].

Male Wistar rats (140 to 150 g) in which the unilateral sciatic nerve had been crushed were treated consecutively with methylcobalamin (5, 50 and 500 mug/kg/day i.p.) or saline immediately after the nerve-crush. Thereafter, they were periodically sacrificed for biochemical and histological examinations. At different intervals after the nerve-crush, L-leucine-4,5-T (20 mu Ci/100g, specific activity 15 mCi/m mole) or L-leucine -14C(U) (15 muCi/100g, specific activity 270 mCi/m mole) was given i.p. to some rats of each group and 3 hr later they were sacrificed to determine the rate of leucine incorporation into protein fractions of the crushed nerve and the denervated muscles. The nerve and muscles of the contralateral side served as control. Longitudinal sections of proximal and distal stumps of the sciatic nerve were prepared and stained with hematoxylin and eosin. As compared with saline group, repeated injections of 5, 50 and 500 mug/kg/day of methyl-cobalamin caused a significant increase of the in vivo incorporation of radioactive leucine into the protein fraction of the crushed sciatic nerve 5 to 7 days after the crush. In contrast, a recovery of the increased incorporation of leucine into the crushed nerve was more rapid in methylcobalamin groups than in the saline group. On the other hand, methylcobalamin (5 approximately 500 mug/kg/day i.p.) had no significant effect on the leucine incorporation into the denervated muscles (m. gastrocnemius, m. tibialis anterior and m. soleus). In addition, consecutive injections of methylcobalamin (5 approximately 500 mug/kg/day) did not affect the mitosis of Schwann cells during the period of Wallerian degeneration of the crushed sciatic nerve. These results suggest that methylcobalamin possesses a stimulating effect on proteosynthesis in Schwann cells at the initial stage of axon regeneration and it may facilitate neural regeneration.

Animals↗