Structure and analgesic activity relationship of cyclo-tyrosyl-arginyl and its three stereoisomers.
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Analgesics↗
Biomedical subjects
S Sakurada
Publications and source records attributed to S Sakurada.
Head-twitch response induced by tyramine.
The intracerebroventricular (IC) administration of tyramine (TyA) induced a characteristic head-twitch response in mice pretreated with safrazine, a monoamine oxidase inhibitor. Safrazine-pretreated mice exhibited similar head-twitches following the IC treatment of serotonin (5-HT). The maximum dose of 5-HT which did not elicit head-twitches significantly potentiated TyA-induced head-twitches. Antiserotonergic drugs such as morphine and dimethothiazine antagonized TyA-induced head-twitches. A serotonergic denervator, 5,6-dihydroxytryptamine, potentiated head-twitch induced by TyA or 5-HT. Both TyA-induced and 5-HT-induced head-twitches were inhibited by dopamine and noradrenaline, while catecholaminergic denervators such as reserpine and 6-hydroxydopamine, and diethyldithiocarbamic acid, a dopamine-beta-hydroxylase inhibitor, increased the TyA response. These results indicate that head-twitches induced by TyA may be mediated via the serotonergic system and may inhibit the catecholaminergic system.
5,6-Dihydroxytryptamine↗
Effects of morphine on evoked potentials recorded from the amygdala by tooth pulp stimulation in cats.
Effects of intravenously administered morphine on the evoked potentials of the amygdala elicited by tooth pulp stimulation were examined in cats. The various evoked potentials were observed in regions of the amygdala such as nucleus amygdaloideus centralis (pars lateralis), nucleus amygdaloideus basalis (pars magnocellularis), nucleus amygdaloideus basalis (pars parvocellularis) and nucleus amygdaloideus lateralis. Evoked potentials were significantly decreased by morphine in four of the recorded regions. Morphine had no effect on the latency at any site of the amygdala observed. Depressant effects of morphine on evoked potentials were antagonized by naloxone in all 14 cats. This study indicates that there is a receptive field of pain in the amygdala which undoubtedly plays a role in emotion.
Amygdala↗
Excitatory effects of dihydrocapsaicin on nociceptive neurons in the medial thalamus.
Effects of capsaicin and dihydrocapsaicin, which are pungent substances contained in Capsicum annuum L., were studied in 32 gallamine triethiodide immobilized cats. Single units were recorded from the medial thalamus using stainless steel microelectrodes. Of the 56 neurons recorded, 28 were responsive to both noxious (pinching) and non-noxious (hair and/or tapping) stimuli, while 16 were activated only by non-noxious stimuli. The remaining 12 neurons did not respond to any natural stimulus. Somatic receptive fields of nociceptive and non-nociceptive neurons were found to be widely distributed over the whole body. Twenty-six of 28 nociceptive neurons were activated by an intra-arterial administration of bradykinin, capsaicin and dihydrocapsaicin. Fourteen of 16 non-nociceptive neurons were not activated by these substances. The mean latency and duration of bradykinin were 8.7 and 12.5 sec, those of capsaicin were 1.2 and 6.1 sec and those of dihydrocapsaicin were 1.3 and 5.0 sec, respectively. The increase of firing frequency produced by capsaicin and dihydrocapsaicin was inhibited by morphine and this inhibition was antagonized by naloxone. However, the activity of medial thalamic neurons with non-noxious stimuli was not affected by these drugs. These results suggest that the pain-conducting fibers were selectively activated by capsaicinoids as well as by bradykinin.
Action Potentials↗
[The effect of thiamine deficiency on the actions of drugs affecting the central nervous system in rats (author's transl)].
Male Wistar rats, 35-days-old, maintained on a thiamine deficient diet for 30 days showed marked growth inhibition and a heart rate less than 70% of that of control rats. We examined the effect of thiamine deficiency on the action of drugs effecting the central nervous system at this period. In thiamine deficient rats treated with chloral hydrate 200 mg/kg, ketamine 100 mg/kg sodium pentobarbital 50 mg/kg, and hexobarbital 100 mg/kg, the sleeping time increased. Pretreatment with 15 mg/kg of the metabolic enzymes inhibitor, SKF-525A, 30 min prior to the hexobarbital administration resulted in prolongation of sleeping time in all groups. The thiamine deficient rats slept almost 3.5 times longer than did the control group. Pretreatment with 100 mg/kg of the metabolic enzyme inducer, sodium phenobarbital, 48 hours prior to hexobarbital treatment resulted in decreased sleeping time in all groups, as compared with only hexobarbital treatment. In the thiamine deficient rats the catalepsy and ptosis induced by the i.p. administration of tetrabenazine 50 mg/kg was reduced even when the control and pair-fed groups responded to this drug at the drug peak time. The spontaneous neuronal activity of lateral hypothalamus was most sensitive to the administration of 5-hydroxytryptophan in thiamine deficient rats.
5-Hydroxytryptophan↗
Microassay of adenine nucleotides in intima and media of the aortic wall.
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Adenosine Diphosphate↗
[Effects of d-pseudoephedrine on tracheo-bronchial muscle and the cardiovascular system (author's transl)].
The action of d-psuedoephedrine on bronchial smooth muscle, respiratory resistance and blood pressure was compared with that of 1-ephedrine. The following results were obtained. 1) Administration of dl-isoproterenol on isolated guinea pig tracheal muscle previously constricted with acetylcholine (ACh) or histamine (his) was the most effective and d-pseudoephedrine had the same effect as 1-ephedrine. The relaxing effect of dl-isoproterenol, 1-ephedrine or d-pseudoephedrine on ACh or His induced tracheal constriction was competitively antagonized by the pretreatment of propranolol. 2) The intravenous or sublingual administration of d-pseudoephedrine on the increased respiratory resistance induced by His produced the same effect as 1-ephedrine. 3) The increase in blood pressure with d-pseudoephedrine was weaker than that of 1-ephedrine. 4) When 1-ephedrine of d-pseudoephedrine was repeatedly injected into the same animal, signs of tachyphylaxis were observed. It was found that d-pseudoephedrine, the main alkaloid of Ephedrine Helba, exhibited the relaxing effect on bronchial smooth muscles as did 1-ephedrine. The respiratory resistance increased by His was inhibited by the sublingual administration of d-pseudoephedrine and 1-ephedrine.
Administration, Oral↗
[Effects of morphine on the single unit activity of nucleus dorsal raphe].
Effects of morphine were studied in 36 gallamine triethiodide immobilized adult cats under light N2O anesthesia. Single units were recorded from the nucleus dorsal raphe using a stainless steel microelectrode. Dorsal raphe neurons were divided into two types; one was a clock-like (CL) neuron which was typically slow in rate, rhythmic and stable throughout recording time, and the other was a non-clock like (NCL) neuron which was relatively irregular in pattern as compared with CL neuron. Out of 36 neurons recorded in this experiment, 13 were CL neurons and 23 were NCL neurons. Mean discharge rates (spikes per sec) of CL neuron and NCL neuron were 2.84 (range of 2.01 approximately 3.68) and 4.11 (range of 0.10 approximately 35.09), respectively. None of the 13 CL neurons responded to the nociceptive (pinch and/or brdaykinin) and non-nociceptive (hair bending and/or tapping) stimuli. On the contrary, out of 23 NCL neurons, 13 responded to both nociceptive and non-nociceptive stimuli, 4 were responsive to only non-nociceptive stimuli and 6 were not responsive to these stimuli. Receptive fields of NCL neurons were wide with various somatic modalities. The latency for bradykinin (3 microgram) was 6.46 +/- 0.77 sec. Effects of morphine were examined in 6 CL neurons and 12 NCL neurons. After morphine, no nociceptive neuron responded to nociceptive stimuli, although there was no appreciable change in the responsiveness to non-nociceptive stimuli. Firing frequency and pattern of all CL neurons were unaffected by morphine. Out of 12 NCL neurons, 7 were unaffected in firing frequency and 5 were decreased after morphine.
Action Potentials↗
[Effects of morphine on evoked potential recorded from pain-afferent pathways (author's transl)].
Effects of morphine (1 mg/kg i.v.) were examined on evoked potential of somatosensory afferent pathways elicited by tooth pulp stimulation in cats. Results were as follows: In central gray (CG) of the midbrain which has a triphasic evoked potential with a short latency, morphine decreased the amplitude. In nucl. lateralis posterior(LP) and nucl. medialis dorsalis(MD) of the thalamus, association relay nuclei, which have a late component followed by a fast component with a relatively short latency, morphine decreased the amplitude of the late component but not that of fast component of the evoked potential. In nucl. centralis lateralis(CL) of the thalamus, intralaminar nuclei, and pre-central association area(PCA) of the cortex, which have monophasic and triphasic evoked potentials with a long latency, respectively, morphine markedly decreased the amplitude of both evoked potentials. In nucl. ventralis posteromedialis(VPM) and somatic sensory area I (SI), lemniscal system, which has biphasic and mutiphasic evoked potentials with a short latency, respectively, morphine had no effect on these evoked potentials. As these depressant effects of morphine on evoked potentials were antagonized by naloxone (0.2mg/kg i.v.), a specific morphine action is suggested.
Afferent Pathways↗
[Analgesic effect of pentazocine and its action on nociceptive afferent pathway].
Nociceptive stimulus was applied to the skin of adult cats by pinching with a serrated forceps or by radiant heat with Pain meter. This stimulation caused motor or emotional responses such as movements of the head and trunk, vocalization, escape and attack. After the administration of pentazocine, these responses disappeared and the animals behaved normally. Analgesic action appeared approximately 15 min after the administration and lasted more than 90 min. Effects of pentazocine on pain-afferent pathways were studied and the evoked potential was recorded by tibial nerve stimulation. Though pentazocine did not influence the evoked potential recorded from somatic sensory area I and mesencephalic central gray, the evoked potential in pre-central association area, nucleus centralis lateralis, nucleus suprageniculatus-limitans and reticularis pontis caudalis was reduced by pentazocine.
Afferent Pathways↗
[Central effects of beta-phenylethylamines. (8). Increase in spontaneous motor activities of mice caused by intracerebrally administered metaramino].
Metaraminol (MA) (40, 80 and 160 microng) was injected i.c. into mice and spontaneous motor activity (SMA) measured by photo-cell counters method was found to increase 30 min after the injection. Ninety min after, the SMA was restored to the saline treated control. MA (80 microng i.c.) was also injected into isocarboxazide (Iso) pretreated mice and the SMA markdly increased as compared with the Iso+saline treated group or tween+MA treated group. When MA was injected i.c. into alpha-methyl-p-tyrosine (alpha-MT) pretreated mice, the SMA significantly increased as compared with that of the alpha-MT+saline treated group, but there was a decrease as compared with that of the tween+saline or tween+MA treated group. In alpha-MT treated mice. L-Dopa restored the hyper-motor activity of animals treated with MA. Diethyldithiocarbamate (700mg/kg i.p.) had no influence, whereas haloperidol markedly blocked the hyper-motor activity induced by MA. The hyper-motor activity induced by MA in mice raised the question of a possible role of noradrenaline and dopamine in the mediation of this action.
Animals↗
On the brain monoaminergic systems relating to ejaculation. I. Brain dopamine and ejaculation.
The effects of psychotropic drugs on ejaculation in dogs and on brain monoamines in dogs and rats were investigated. The results obtained in this study indicate that ejaculation is activated by the dopaminergic system in the brain, and that dopamine in the anterior hypothalamus is closely related to the occurrence of ejaculation.
Animals↗
[Central action of beta-phenylethylamine derivatives. (7) Effects of intracerebral administration of tyramine on brain monoamine levels in mice].
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Animals↗
[Effects of MS4101, a new benzodiazepine compound, on evoked potentials induced by noxious stimulation of hind legs in cats].
The effects of 10-chloro-11b-(2'-fluorophenyl)-2,3,5,6,7,11b-hexahydro-7-(2''-hydroxyethyl)benzo[6,7]-1,4-diazepino [5,4-b]oxazol-6-one (MS4101), a new benzodiazepine compound, on evoked potential in cats were examined and compared with diazepam. Though evoked potential in somatic cortex I, motor cortex I and posterior groups induced by tibial nerve stimulation were unaffected by a small dose of MS4101 (1 mg/kg) which did not influence on limbic system, the amplitude of evoked potential in midbrain reticular formation was reduced. The amplitude of evoked potential in amygdala and hippocampus induced by cutaneous nerve stimulation was reduced by MS4101 and diazepam. These two drugs had the same effect on amygdala and difference in the degree of action between these drugs was not observed. Sham rage response following head shake, circling and whine behaviour was observed by electrical stimulation of the hypothalamus. The threshold of sham rage response by raised by MS4101 and diazepam.
Animals↗
[Effects of a benzodiazepine derivative, MS4101, on emotional behaviour of untamed cats].
Effects of MS4101 on emotional behaviour in untamed cats were studied and compared with those of diazepam. Offensive behaviour, i.e., whine response to a rod presented in front of the snout and blowing air on back hair was markedly observed, and whine, attacking and biting responses to tapping with a rod on the back in these cats were marked. Defensive behaviour, i.e., hissing, crouching body, ear flattening to blowing air on back hair, a rod presented and tapping was markedly observed. From 30 min after MS4101 and diazepam in doses of 2 approximately 4 mg/kg i.p., offensive behaviour in untamed cats was depressed. ID50 (50% of inhibition dose) of offensive behaviour for MS4101 and diazepam was 2.40 (1.95 approximately 2.95) mg/kg i.p. and 0.96 (0.69 approximately 1.34) mg/kg i.p., respectively. MS4101 and diazepam in doses of 2 approximately 4 mg/kg i.p. decreased the offensive behaviour. ID50 of defensive behaviour for MS4101 and diazepam was 3.00 (2.46 approximately 3.66) mg/kg i.p. and 1.45 (1.14 approximately 1.84) mg/kg i.p., respectively. Both MS4101 and diazepam exhibited muscle relaxant effects. Here, diazepam was more effective than MS4101. ED50 of muscle relaxant activity for MS4101 and diazepam was 4.30 (3.03 approximately 6.11) mg/kg i.p., 7.40 (5.04 approximately 10.66) mg/kg i.p., respectively. A single administration of MS4101 and of diazepam in doses 2 mg/kg i.p. enhanced food intake.
Agonistic Behavior↗
[Central action of beta-phenylethylamine derivatives. (4) Effects on spontaneous motor activity and body temperature of beta phenylethyamine derivatives injected into the brain in reserpine pretreated mice].
Effects on spontaneous motor activity and body temperature of beta-phenylethlamine derivatives injected into the cerebral ventricles in reserpine or reserpine and isocarboxazide pretreated mice were investigated with the following results. 1) Each injection of tyramine (40 mug) and dopamine (40 mug) increased the spontaneous motor activity measured by the photo-cell counters method in reserpinized mice. 2) Each injection of tyramine (40 mug), dopamine (40 mug) and beta-phenylethylamine (40 mug) increased the spontaneous motor activity measured by both the wheel cage and photo-cell counters methods in reserpine and isocarboxazide-pretreated mice, but noradrenaline (20 mug) and isoproterenol (80 mug) did not increase the spontaneous motor activity as determined by both methods. 3) The injection of tyramine (40 and 80 mug), dopamine (10 and 40 mug) and p-octopamine (40 mug) increased the body temperature in reserpine and isocarboxazide pretreated mice. 4) Tyramine, dopamine and p-octopamine caused a marked increase in the body temperature as compared with control injection in reserpine and isocarboxazide-pretreated mice, whereas isoproterenol had no influence on body temperature. Our results suggest that beta-phenylethylamine derivatives have different effects in reserpinized and non-pretreated states.
Animals↗
[Effect of beta-phenylethylamine derivatives on the central nervous system. II. Pharmacological effect of the intracerebral administration of metaraminol on the central nervous system].
Six hours after intracerebral administration, the central effects of metaraminol were examined with the following results. 1) Metaraminol in doses of 40 approximately 160 mug decreased spontaneous motor activity in mice as measured by the photo-cell counters method, the wheel cage method or the open-field test. Ptosis and catalepsy induced at these doses. 2) Metaraminol in doses of 40 approximately 80 mug which influenced the spontaneous motor activity in mice, blocked the avoidance behaviour but not escape. 3) Metaraminol in doses of 1.25 approximately 10 mug which did not influence the spontaneous motor activity in mice, markedly blocked the attaching response induced by the electroshock. 4) Ten min after intraventricular administration, metaraminol in a dose of 500 mug induced the arousal pattern of EEG in sensory cortex of cats and this pattern lasted for 30 min. Ninety min after administration, EEG tracings reverted to the drowsy pattern.
Aggression↗
[Effect of beta-phenylethylamine derivatives on the central nervous system. III. Motor activity changes in mice due to the intracerebral administration of metaraminol].
Influence of metaraminol on behavioural changes in mice was studied with the following results. 1) When metaraminol was injected i.c., spontaneous motor activity as tested by either the photocell counters method or open-field test markedly increased within 90 min after injection, while on the contrary greatly decreased 3 hr later as compared with control group. Thus, these biphasic effects of metaraminol were clearly established. 2) 30 min after injection, metaraminol in doses of 160 mug did not alter brain catecholamines in mice, however, 6 hr after injection, brain dopamine and norepinephrine markedly decreased. 3) When metaraminol was injected into mice pretreated with reserpine of 6-hydroxydopamine, spontaneous motor activity tested by photo-cell counters method markedly increased and anti-6-hydroxydopamine activity of metaraminol was stronger than anti-reserpine. 4) Metaraminol completely antagonized ptosis and catalepsy induced by rerserpine. 5) Six hr after injection, anti-methamphetamine activity was observed.
Animals↗