Search PubMed⌕ Search

Biomedical subjects

K Kisara

Publications and source records attributed to K Kisara.

At least 145 records · Page 8Linked to original sources
PubMed1985

Antinociceptive properties of a new tetrapeptide, Asn-Ala-Gly-Ala, in mice.

The effect of intracerebroventricularly (i.c.v.) administered Asn-Ala-Gly-Ala (NAGA), a partial sequence of beta-lipotropin, was investigated using the tail-pressure, hot-plate and phenylbenzoquinone (PBQ)-induced writhing tests in mice. I.c.v. administration of NAGA produced a dose-dependent inhibition of responses as measured by the three different assays. The ED50 of NAGA on the tail-pressure test did not differ from that obtained on the hot-plate test. NAGA showed a prominent reduction in activity on the PBQ writhing as compared with the hot-plate and tail-pressure tests. A low dose of naloxone (0.1-1.0 mg/kg, s.c.) resulted in a dose-dependent antagonism of the effect of NAGA in all assays. These data suggest that the antinociceptive effect induced by NAGA may involve the endogenous opioid system in mice.

Analgesics↗
PubMed1984

D-Arg2-dermorphin tetrapeptide analogs: a potent and long-lasting analgesic activity after subcutaneous administration.

To examine pharmacological properties of D-Arg2-dermorphin tetrapeptides, six tetrapeptide analogs based on the following formulas, H-Tyr-D-Arg-Phe-Gly-OX (X = H, ethyl, n-propyl), H-Tyr-D-Arg-Phe-Sar-OX (Sar = sarcosine; X = H, methyl, ethyl), were prepared. All these analogs exhibited highly potent and long-lasting analgesia as compared with that of morphine after subcutaneous administration in mice. Among analogs tested, H-Tyr-D-Arg-Phe-Sar-OH showed the highest activities, which were 21, 30 and 58 times more active than morphine in the tail pressure, tail flick and phenylbenzoquinone writhing tests, respectively, on a molar basis.

Analgesics↗
PubMed1984

Antinociceptive effects of neonatal capsaicin in rats with adjuvant arthritis.

Rats were treated with capsaicin (50 mg/kg, SC) either on the second day or on the second and third days of life. A significant attenuation of the responses to noxious stimuli was obtained in the capsaicin treated animals as measured by the hot-plate or paw pressure tests but not by the tail-flick test. Furthermore, neonatal capsaicin produced a significant reduction of response in the formalin test. Capsaicin reduced the reaction latency in rats with adjuvant arthritis as measured by the hot-plate and paw pressure tests, though capsaicin did not alter the overall time course of the response to Freund's adjuvant. Capsaicin also attenuated the weight loss or the decreased ambulatory and rearing behaviours which occurred in the control animals with adjuvant arthritis. It is suggested that neonatal treatment with capsaicin may relieve the responsiveness to long-lasting nociceptive stimuli by adjuvant in rats.

Analgesics↗
PubMed1984

Comparison of the antinociceptive effects of intracerebroventricular injection of kyotorphin, cyclo (N-methyl-Tyr-Arg) and Met-enkephalin in mice.

Intracerebroventricular (i.c.v.) administration of kyotorphin (L-Tyrosine-L-Arginine) or Metenkephalin (Met-ENK) to conscious mice resulted in a dose-dependent antinociceptive effect as measured by three pain tests. Cyclo(N-methyl-L-Tyrosine-L-Arginine) (cyclo NMTA), an analogue of kyotorphin, increased the reaction time in the tail-pressure and tail-flick tests. Both dipeptides also decreased writhing induced by acetic acid. However, the antinociceptive activity of cyclo NMTA was substantially greater than that of kyotorphin or Met-enkephalin. At the maximum effective dose of 62.7 nmol/mouse, this cyclic dipeptide produced a more long-lasting antinociceptive effect than did kyotorphin or Met-enkephalin. Antinociception induced by cyclo NMTA or kyotorphin was significantly reversed by pretreatment with naloxone (2 or 8 mg/kg, i.p.), though naloxone was not as effective an antagonist of the antinociceptive action of these peptides as it was against Met-enkephalin. The results indicate that the antinociceptive effect induced by cyclo NMTA may in part involve the endogenous opioid system in mice.

Analgesia↗
PubMed1984

Comparison of the antinociceptive effect between D-Arg containing dipeptides and tetrapeptides in mice.

D-Arg containing dipeptides, H-Tyr-D-Arg-OMe and H-Tyr (Et)-D-Arg-OMe, and D-Arg2 substituted N-terminal tetrapeptides of dermorphin, H-Tyr-D-Arg-Phe-Gly-OEt and H-Tyr (Et)-D-Arg-Phe-Gly-OEt administered intracerebroventricularly exhibited dose-dependent antinociceptive activities in mice as measured by the tail pressure and phenylbenzoquinone writhing tests. The effects of these peptides used were significantly antagonized by the pretreatment with naloxone, indicating that these effects must be produced through opioid receptors. Furthermore, it is of conspicuous interest that the effects of tetrapeptides revealed in infinitestimal order (ED50 = 12.5 and 355.0 pmole in the tail pressure test and 3.1 and 53.0 pmole in the phenylbenzoquinone writhing test, respectively) and was much more potent and prolonged than those of morphine, not to mention dipeptides used. However, judging from the difference of peak times and the degree of the antagonism by naloxone, it was suggested that dipeptides and tetrapeptides used might act on different sites of action in the central nervous system.

Analgesia↗
PubMed1984

Structure-antinociceptive activity studies with neurotensin.

The antinociceptive effects of synthetic neurotensin (NT), its fragments and analogues administered into the lateral cerebroventricle have been compared in the conscious mouse. Intracerebroventricular (i.c.v.) administration of NT produced a dose-dependent antinociceptive effect in the tail pressure test. The NT fragments and analogues, NT(8-13), NT(8-10), NT(9-13), NT(9-11), NT(8-11) NHEt and NT(9-11) NHEt were also effective antinociceptive peptides. The potency of NT(8-13) and the duration of its effects were found to be approximately equal to those of NT. The antinociceptive effects produced by NT, NT(8-13) and NT(9-13) were significantly reversed by the opioid antagonist naloxone but not by thyrotropin releasing hormone. It is concluded that NT(8-13) is required for the full expression of the antinociceptive effects of NT which may be mediated in part through the brain opioid system.

Analgesics↗
PubMed1984

Potentiation of cyclo (N-methyl-Tyr-Arg)-induced antinociceptive activity by thyrotropin-releasing hormone in mice.

The effect of thyrotropin-releasing hormone (TRH) and its metabolite, cyclo(His-Pro) (C.HP), on cyclo(N-methyl-Tyr-Arg) (C.NMTA)-induced antinociception as measured by the tail-pressure test in mice has been examined. C.NMTA-induced antinociception was significantly potentiated by simultaneously intracerebroventricular or intraperitoneal injection of TRH (approximately 20-50%) in a dose-dependent manner, whereas the effect of morphine was not influenced significantly by TRH. C.HP had no significant effect on the antinociceptive response induced by C.NMTA or morphine. It is concluded that the mechanism of C.NMTA-induced antinociception may be involved in TRH neuronal system in the brain.

Analgesics↗
PubMed1984

Comparison of the antinociceptive effect between the cyclic dipeptide cyclo[Tyr(Et)-homoarginine] and the linear dipeptide Boc-Tyr(Et)-homoarginine-OMe in rats.

The antinociceptive effect of the cyclic dipeptide cyclo[Tyr(Et)- homoarginine] (C.TEHA) was examined utilizing the tail flick test and the digitus pinching test in rats in comparison with the linear dipeptide Boc-Tyr(Et)-homoarginine-OMe (B.TEHM). Though both dipeptides administered into the lateral, 3rd and 4th cerebroventricles produced antinociceptive effects equipotent to morphine, except for the 4th cerebroventricular administration of B.TEHM, the administration into the spinal subarachnoid space was without effect. The effect of B.TEHM was completely antagonized by the pretreatment of naloxone (i.p.) when administered into the 3rd cerebroventricle where its effect was demonstrated to be the most potent. However, naloxone had no significant effect on C.TEHA administered into the 3rd cerebroventricle in both tests. It was concluded that both dipeptides act on the upper brain stem, especially around the 3rd cerebroventricle. Moreover, it was also thought that the effect of B.TEHM may be involved in the brain opioid system, and that of C.TEHA can be produced via a naloxone-resistant opioid system or a non-opioid system.

Analgesics↗
PubMed1983

Antinociceptive effect of centrally administered cyclo(N-methyl-L-Tyr-L-Arg) in the rat.

The tail-flick test was used to test cyclo(N-methyl-L-Tyr-L-Arg) (C.NMTA), kyotorphin (L-Tyr-L-Arg) and morphine for antinociceptive effects following injection into the cerebroventricles (lateral ventricle (VL), third ventricle (V3) and fourth ventricle (V4)) and into the spinal subarachnoid space in the rat. When injected into the VL, V3 and V4, but not into the spinal subarachnoid space, C.NMTA produced a dose-dependent inhibition of the tail-flick response to thermal stimulation. The ED50 values for each site were 61.0 (48.0-77.5), 40.0 (27.4-58.4) and 163.0 (86.7-306.4) nmol/rat, respectively. Behavioral sedation was seen when C.NMTA was injected into the VL, V3 and V4, but not into the spinal subarachnoid space. Kyotorphin was without antinociceptive effect when given by all routes. However, weak sedation was seen after injection into the cerebroventricles. Naloxone (2, 4 and 20 mg/kg), an opiate antagonist, injected intraperitoneally (i.p.) 20 min before C.NMTA injection, did not significantly alter the C.NMTA-induced antinociceptive effect. Additionally, naloxone (2, 4 and 20 mg/kg i.p.) did not abolish the sedative effect of this peptide. It is suggested that C.NMTA produced a naloxone-resistant antinociceptive effect mainly on the upper brain stem.

Analgesics↗
PubMed1983

[The involvement of the cholinergic system in the tremor induced by phenol].

The effect of cholinergic drugs on the tremor induced by subcutaneous (s.c.) injection of a 1 v/v% phenol solution was investigated. Male dd-Y strain mice weighing 18-24 g were used in all experiments. Intraperitoneal (i.p.) administration of physostigmine (0.05-0.1 mg/kg) did not alter the tremor. Neostigmine (0.05-0.1 mg/kg i.p.) increased the strength of the tremor weakly and shortened the latency of the tremor. I.p. administrations of methacholine, atropine, methylatropine, and scopolamine did not produce significant effects on the tremor. I.p. injection of nicotine (0.5-1 mg/kg) shortened the duration of the tremor. Intracerebro-ventricular (i.c.v.) infusions of nicotine (4 micrograms/mouse) and carbachol (5 micrograms/mouse) prolonged the latency of the tremor. Furthermore, i.c.v. infusion of nicotine (4 micrograms/mouse) reduced the strength of the tremor slightly. On the contrary, i.p. (10-20 mg/kg) or i.c.v. (20-60 micrograms/mouse) administration of mecamylamine potentiated the strength and prolonged the duration of the tremor in a dose dependent manner. Hexamethonium (10-20 micrograms/mouse, i.c.v.) also potentiated the strength and prolonged the duration of the tremor. These results suggest that a peripheral increase of acetylcholine level may potentiate the tremor induced by phenol, and the tremor may be suppressed by a negative feedback mechanism involving the nicotinic cholinergic system of the central nervous system.

Animals↗
PubMed1982

A possible mechanism of the tyramine-induced head-twitch response.

The effects of monoaminergic drugs on the head-twitch response (HTR) induced by intracerebroventricular (i.c.v.) injection of tyramine (TyA) in mice pretreated with safrazine, a monoamine oxidase inhibitor, were compared with effects on the response induced by the i.c.v. injection of serotonin (5-HT) in safrazine-pretreated mice. The HTR induced by both TyA and 5-HT were suppressed by i.p. injection of p-chlorophenylalanine. Chlorimipramine enhanced the 5-HT response but not the TyA response. Dimethothiazine, a serotonergic blocker, reduced both the TyA and 5-HT responses. The i.c.v. injection of p-chlorophenylalanine methylester resulted in a reduction of the TyA response but not of the 5-HT response. The i.c.v. injection of 5,6-dihydroxytryptamine (5,6 DHT) 1 day before the test suppressed the TyA response but enhanced the 5-HT response. The i.c.v. injection of noradrenaline reduced both the TyA and 5-HT responses. The i.c.v. injection of 6-hydroxydopamine, and i.p. injection of alpha-methyl-p-tyrosine and tolazoline accelerated the TyA response. These results suggest that the TyA response may be based on the release of endogenous 5-HT and can be suppressed by the catecholaminergic system.

5,6-Dihydroxytryptamine↗
PubMed1982

Intracranial injection of thyrotropin releasing hormone (TRH) suppresses starvation-induced feeding and drinking in rats.

The sites at which TRH produces suppression on feeding and drinking were examined anatomically in the rat brain. This was accomplished by microinjecting nmol concentration of TRH into 6 different brain sites. Intracerebroventricular injection of TRH (25, 50, 100 nmol/rat) suppressed starvation-induced feeding and drinking in a dose related manner. The microinjection in a small amount of TRH (8 nmol/hemisphere) into the medial and lateral hypothalamus produced relatively severe anorexia and adipsia as compared with the other areas including the nucleus accumbens, the substantia nigra, the globus pallidus and the amygdala. It was concluded that the medial hypothalamus is the most sensitive site of TRH-induced anorexia and adipsia and the action of TRH on the lateral hypothalamus is also a possible mechanism mediating the decrease in water intake.

Amygdala↗
PubMed1982

Potentiating effects of prostaglandin E2 on bradykinin and capsaicin responses in medial thalamic nociceptive neurons.

Potentiating effects of prostaglandin E2 (PGE2) on bradykinin and capsaicin responses were studied in 34 gallamine triethiodide immobilized cats. Single neurons were recorded from the medial thalamus by using stainless steel microelectrodes. The animals were given agents into the femoral artery through a retrogradely inserted cannula. Of the 22 neurons responding to bradykinin, 13 were potentiated by the injection of PGE2, and the remaining 9 neurons were ineffective. Nine of the 17 neurons responding to capsaicin were also potentiated by PGE2. PGE2 significantly shortened the mean latency of bradykinin to fire the neuronal activity without changing the duration, but with the injection of capsaicin, there was no change in latency and duration in the presence of PGE2. Aspirin suppressed the increased activity of the medial thalamic neurons produced by bradykinin, and this suppression was antagonized by arterial infusion of PGE2. However, the activity of medial thalamic neurons with capsaicin was scarecely affected by aspirin. These results suggest that the bradykinin-induced activity of medial thalamic neurons may be mediated by PGE2 and that the mechanism of activation of nociceptive neurons produced by capsaicin is different from that of bradykinin.

Action Potentials↗
PubMed1982

Effects of morphine on single unit activity of the amygdala in cats.

Single neuronal activity has been recorded extra-cellularly from the nucleus amygdaloideus centralis (pars lateralis) (Acl), the nucleus amygdaloideus centralis (pars medialis) (Acm), the nucleus amygdaloideus basalis (pars magnocellularis) (Abm), the nucleus amygdaloideus lateralis (Al), and the nucleus amygdaloideus basalis (pars parvocellularis) (Abp). The majority of the Acl, Acm, and Abm neurons were excited by nociceptive stimulation such as pinching the skin with serrated forceps and/or intraarterial injection of bradykinin. The nociceptive neurons were also driven by non-nociceptive stimulation such as tapping of deep tissues and bending hairs with an air-puff. Their receptive fields were large. After the intravenous administration of morphine, all nociceptive neurons became unresponsive to nociceptive stimuli, although they were driven by non-nociceptive stimuli. Intravenous naloxone antagonized the antinociceptive action of morphine. This suggests that morphine has selective and inhibitory effects on impulse transmission to these nociceptive neurons, and the amygdala, especially the Acl, Acm, and Abm, plays an important role in central nociceptive processing.

Amygdala↗
PubMed1982

[Effects of methyl o-(4-hydroxy-3-methoxycinnamoyl) reserpate (CD-3400) on erection and ejaculation in dogs].

Effects of methyl o-(4-hydroxy-3-methoxycinnamoyl)reserpate (CD-3400), a new antihypertensive agent belonging to the class of rauwolfia alkaloids, on erection and ejaculation in dogs were investigated and compared with such effects of reserpine and rescinnamine in dogs. A single dose of CD-3400 (0.125 mg/kg) administered orally to normal dogs produced no effects on erection and ejaculation, although the same dose of reserpine and rescinnamine resulted in a marked suppression of only ejaculation at 24 and 48 hr after administration. CD-3400 (0.5 mg/kg) administered orally, as well as reserpine (0.125 mg/kg) and rescinnamine (0.125 mg/kg) suppressed ejaculation at 24 hr after administration; however, the suppressive effect of CD-3400 on ejaculation was weaker and shorter than that of reserpine or rescinnamine and recovered 96 hr after administration. The order of the suppressive effect of the agents was as follows: reserpine greater than rescinnamine greater than CD-3400. Repeated administration of reserpine (0.01 mg/kg/day p.o.) for 20 days, produced a marked suppressive effect on ejaculation, whereas the effect of CD-3400 (0.06 mg/kg/day p.o.) was also weaker than that of reserpine. 24 hr after oral administration in a single dose of CD-3400 (0.5 mg/kg), reserpine (0.125 mg/kg) or rescinnamine (0.125 mg/kg), the ratios of dopamine (DA) to serotonin (5-HT) in the anterior hypothalamus and hippocampus were decreased significantly as compared with the control. These results indicate that CD-3400 results in a weaker suppressive effect on ejaculation as compared to reserpine and rescinnamine, and CD-3400-induced suppression may be due to a decrease in the ratio of DA to 5-HT in the anterior hypothalamus and hippocampus.

Administration, Oral↗
PubMed1982

[Effect of d-pseudoephedrine on the central nervous system in mice].

Some pharmacological actions of intraperitoneally (i.p.) administered d-pseudoephedrine (d-pseudo) on the central nervous system of mice were compared with those of l-ephedrine (l-eph). Locomotor activity was increased by l-eph (50, 100 and 200 mg/kg,) but not by d-pseudo (50, 100 and 200 mg/kg). Wheel-revolving activity was reduced by a 200 mg/kg dose of both drugs. Rectal temperature was increased by l-eph at 50, 100 and 200 mg/kg. However, it was decreased by 50 and 100 mg/kg doses of d-pseudo, and the change in response to 200 mg/kg of d-pseudo was biphasic, decreasing first and increasing subsequently. Pentobarbital-induced sleeping time was shortened by l-eph (50 and 100 mg/kg), but was not influenced by any of the doses of d-pseudo. In the experiment on locomotor activity, L-3,4-dihydroxyphenylalanine (400 mg/kg, i.p.) potentiated the effects of d-pseudo and l-eph, but reserpine (1 mg/kg, day X 5 days, i.p.) and 6-hydroxydopamine (40 micrograms/mouse, intracerebroventricular injection) potentiated only the effect of l-eph. These results suggest that the effect of d-pseudo on the central nervous system of mouse is not only weaker than that of l-eph, but also the mechanisms of action of these two substances are different.

Animals↗