Biomedical subjects

N Nakamizo

Publications and source records attributed to N Nakamizo.

At least 19 recordsLinked to original sources

PubMed1992

[Herpes zoster of the right cervical region associated with right facial nerve palsy and hoarseness].

A 69-year-old man was suffering from herpes zoster on his 2nd and 3rd right cervical spinal segments and 3rd branch of the trigeminal nerve. He came to our hospital on his 10th illness day and was treated with continuous cervical epidural block, intravenous infusion of acyclovir for five days, and oral paramethasone and Vitamin B12. Oh his 18th illness day, right facial nerve palsy and hoarseness became clear. His cerebrospinal fluid showed no abnormality except cell count 23 x 3 mm-2. No clear paralysis of vocal cords was detected on laryngoscopy. He was also treated with right stellate ganglion block starting on his 21st illness day. His pain and facial nerve palsy recovered completely by his 68th illness day, but hoarseness continued about two months. The hoarseness might be a result of spread of the disease 1) by cerebrospinal fluid, 2) by contact with the 3rd cervical nerve and vagal nerve via accessory nerve, and 3) direct effect on the vocal cords and the muscles controlling them. Herpes zoster on the head and neck region shows various complications and we should follow its course cautiously.

Aged↗

PubMed1992

[Hemodynamic effects of induced hypotension by ketanserin in anesthetized dogs].

Hemodynamic effects of hypotension induced by ketanserin were investigated in 18 mongrel dogs under 0.87% halothane in oxygen (1 MAC). They were randomly allocated to one of two groups. Group C (n = 9) received no vasodilator therapy and served as a control and group K (n = 9) received 0.1% ketanserin solution. Mean arterial pressure decreased and was maintained at 60 mmHg for 60 minutes in group K. No change was noted in hemodynamic variables measured in group C throughout the experiment. During and after induced hypotension in group K, stroke volume index increased significantly compared with the control value. On the other hand, systemic vascular resistance was significantly reduced, reaching 50% of the control value at the end of the hypotensive period. Left ventricular maximum dp/dt showed a significant reduction during hypotension but then increased gradually to the control value. In addition, heart rate decreased significantly during and after induced hypotension, therefore these vasodilator effects were not accompanied by reflex tachycardia. Cardiac index remained unchanged throughout the experiment. Further, no changes in central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure and pulmonary vascular resistance were observed. In conclusion, the data indicate that ketanserin is a potent systemic vasodilator producing stable hemodynamics. It also reduces systemic vascular resistance without reflex tachycardia and this is a favorable effect of ketanserin.

Animals↗

PubMed1992

[Endocrine effects of induced hypotension by ketanserin in anesthetized dogs].

Plasma levels of catecholamines, aldosterone and cortisol as well as plasma renin activity during hypotension by ketanserin were studied in 9 mongrel dogs under 0.87% halothane in oxygen (1MAC). Mean arterial pressure was reduced and maintained at 60 mmHg for 60 minutes by the infusion of 0.1% ketanserin solution. Plasma norepinephrine decreased progressively during hypotension to 35% of the control value after induced hypotension. In contrast, plasma epinephrine increased three-four folds compared with the control value during and after induced hypotension, but this change was not statistically significant. Plasma renin activity and plasma aldosterone showed a slight increase during hypotension but returned toward the control value after discontinuing the infusion of ketanserin. Plasma cortisol remained unchanged throughout the experiment. In conclusion, our data show that hypotension by ketanserin is not accompanied by the activation of the renin-angiotensin-sympathetic system or adrenocortical system.

Animals↗

PubMed1991

[Endocrine effects of hypotension induced by diltiazem in rabbits].

Endocrine effects of hypotension induced by diltiazem, a calcium antagonist, were studied in 16 male rabbits under the inhalation of 0.7% halothane in oxygen. They were randomly allocated to one of two groups. Group C (n = 8) received no vasodilator therapy and served as control and group D (n = 8) received infusion of diltiazem. Mean arterial pressure was decreased and was maintained at 60 mmHg for 60 minutes in group D. No change was noted in plasma catecholamines measured in group C throughout the experiment but plasma renin activity decreased progressively. During and after induced hypotension in group D plasma epinephrine showed a dramatic rise compared with the control value. The maximum increase occurred 30 minutes after induction of hypotension but this change was not statistically significant. Plasma norepinephrine in group D was significantly higher than the control value. Compared with the control value (0.19 +/- 0.04 ng.ml-1), plasma norepinephrine was activated 30 and 60 minutes after induction of hypotension (0.71 +/- 0.16 ng.ml-1, P less than 0.05, 0.82 +/- 0.20 ng.ml-1, P less than 0.05, respectively). Plasma renin activity in group D was significantly higher than the control value. The highest level of plasma renin activity was three times the control value 30 minutes after induction of hypotension. In conclusion, our data show that induced hypotension by diltiazem activates the renin-angiotensin-sympathetic nervous system.

Animals↗

PubMed1991

[A comparison of the endocrine effects of hypotension induced by nicardipine with those by sodium nitroprusside in dogs].

Plasma catecholamines, plasma renin activity, plasma aldosterone and plasma cortisol during hypotension induced by sodium nitroprusside and nicardipine were studied in 27 mongrel dogs under 0.87% halothane in oxygen. They were randomly divided into three groups: sodium nitroprusside (group S: n = 8), nicardipine (group N: n = 8) and controls (group C: n = 9). Group C received no vasodilator therapy and served as a control. Mean arterial pressure was reduced and maintained at 60 mmHg for 60 minutes in hypotensive groups. No changes were noted in plasma catecholamines and plasma cortisol in group C throughout the experiment, but plasma renin activity and plasma aldosterone decreased progressively. During hypotension induced by sodium nitroprusside and nicardipine, plasma epinephrine was significantly higher than the control value. However, after the hypotensive drugs were discontinued, plasma epinephrine decreased slightly. During and after induced hypotension, plasma renin activity of group N and group S were significantly higher than the control values. The highest levels of plasma renin activity 36.7 ng.ml-1.hr-1 in group N and 23.2 ng.ml-1.hr-1 in group S were observed. Plasma aldosterone concentration was significantly higher than the control value in group N. The maximum increase occurred 30 minutes after discontinuation of the nicardipine and the highest concentration of plasma aldosterone was three times control value. In contrast, in group S, plasma aldosterone was unchanged from the control value. Plasma cortisol concentration of group N was significantly increased than the control value. However, in group S, plasma cortisol concentration showed a slight but not significant increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

PubMed1988

Synthesis and antiulcer activity of 5,11-dihydro[1]benzoxepino[3,4-b]pyridines.

A series of substituted 5,11-dihydro[1]benzoxepino[3,4-b]pyridines was synthesized and evaluated for antiulcer activity in water immersion/restrained stress ulcer assay in rats. Structure-activity relationships are described. Most of the tested compounds exhibited low affinity to the muscarinic acetylcholine receptor. The molecular features for the best activities are the 2-(diethylamino)ethylenediamine group at the 5-position of the oxepin ring and an oxepin skeleton rather than a thiepin or a pyran skeleton. Methyl and chlorine substitution on the benzene ring reduced the activity. Compound 11, 5-[[2-(diethylamino)ethyl]amino]-5,11-dihydro[1]benzoxepino [3,4-b]pyridine trihydrochloride was selected for further evaluation. Synthesis and antiulcer activity of optically active 11 is described. There were no statistically significant differences between (+)-, (-)-, and (+/-)-11. Compound 11 showed weak antisecretory activity in pylorus-ligated rats. It is now under clinical evaluation as KW 5805.

Animals↗

PubMed1988

Effects of flunarizine on induced nystagmus and cochlear blood flow.

The effects of flunarizine on induced nystagmus and cochlear blood flow were compared with those of cinnarizine and diphenidol. Flunarizine significantly inhibited caloric (cool water)-induced nystagmus frequency and duration of nystagmus in rabbits at 5 mg/kg i.v., whereas cinnarizine and diphenidol only slightly decreased the frequency of nystagmus at 5 mg/kg, i.v. As for optokinetic stimuli-induced nystagmus in rabbits, flunarizine significantly decreased the amplitude of nystagmus at 2.5 mg/kg i.v., and cinnarizine and diphenidol inhibited nystagmus at 5 mg/kg, i.v. Flunarizine had no effect on nystagmus induced by electrical stimulation of the lateral geniculate body in rabbits at doses up to 5 mg/kg, i.v. Flunarizine increased the cochlear blood flow in anesthetized guinea pigs dose-dependently (0.312-1.25 mg/kg i.v.) On the other hand, cinnarizine (0.625-2.5 mg/kg i.v.) and diphenidol (0.625-2.5 mg/kg i.v.) increased cochlear blood flow, but the duration of action of both cinnarizine and diphenidol was shorter than that of flunarizine at the same dose. As stated above, flunarizine inhibited nystagmus experimentally induced by caloric or optokinetic stimuli. Increased cochlear blood flow suggested that the enhancement of vestibular blood flow might play an important role in the treatment of vestibular dysfunctions with this drug.

Animals↗

PubMed1988

Receptor binding properties of the new calcium antagonist benidipine hydrochloride.

The in vitro receptor binding affinity of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-diyhydropyridine-3, 5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) to 3H-nitrendipine, alpha 1-adrenergic, alpha 2-adrenergic, beta-adrenergic, muscarinic cholinergic, H1-histaminergic, D2-dopaminergic, S2-serotonergic, A1 adenosine and A2 adenosine receptors was compared with that of nifedipine, nitrendipine and nicardipine. KW-3049 bound stereospecifically to 3H-nitrendipine binding sites of rat myocardium with high affinity (Ki = 0.13 nmol/l) and to the rat brain alpha 1-receptor (Ki = 1.2 mumol/l). KW-3049 exhibited no remarkable binding affinity to alpha 2, beta-, D2-, H1-, S2-, A1-, A2- and muscarinic cholinergic receptors at 100 mumol/l. KW-3049 showed competitive inhibition against 3H-nitrendipine binding when it was added simultaneously with the ligand and rat heart membranes. KW-3049 did not affect the dissociation of 3H-nitrendipine from the receptor sites. The inhibitory activity of various isomers of KW-3049 at the 3H-nitrendipine binding sites was shown in the order of S-S-(+) greater than KW-3049 (racemate, S-S-(+), R-R-(-] greater than R-R-(-) greater than S-R-(-) greater than racemate (R-S-(+), S-R-(-] greater than R-S-(+). S-S-(+)isomer was 12 times more potent than R-R-(-)isomer on Ki basis, whereas alpha 1-adrenoceptors followed the order of S-S-(+), R-S-(+), KW-3049, racemate (R-S-(+), S-R-(-], S-R-(-) and R-R-(-).

Animals↗

PubMed1988

Antihypertensive effects of the new calcium antagonist benidipine hydrochloride in rats.

Using spontaneously hypertensive rats (SHR), DOCA-NaCl hypertensive rats (DHR) and normotensive rats (NTR), the antihypertensive action of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dic arb oxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) was comparatively evaluated with those of nicardipine and hydralazine. Administration of KW-3049 at 0.5, 1 and 3 mg/kg (p.o.) showed dose-dependent antihypertensive action. This action appeared gradually and it lasted longer than those of nicardipine and hydralazine. The administration of KW-3049 at 0.5 mg/kg (p.o.) did not show any effect on the blood pressure of NTR, but a long-lasting blood pressure lowering action was observed by the administration at 1 and 3 mg/kg (p.o.). This antihypertensive action specific to the hypertensive animals was similar to that of nicardipine, however, it was different from that of hydralazine, with which the blood pressure in SHR, DHR and NTR was lowered in similar degrees. Also, administration of KW-3049 caused tachycardia concomitant with the fall of blood pressure, however, it was mild as compared with those of nicardipine and hydralazine. When KW-3049 at doses of 3 and 10 mg/kg (p.o.) once a day was continuously administered to SHR for 31 days and changes of the antihypertensive action were observed, no tolerance developed and rebound hypertension following the discontinuation of medication did not occur. When the effect on the urinary volume and electrolyte excretion was evaluated in rats loaded with physiological saline solution, a natriuretic effect was observed by the administration of KW-3049 at 0.5, 1 and 3 mg/kg (p.o.).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Synthesis and pharmacological activity of stereoisomers of 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid methyl 1-(phenylmethyl)-3-piperidinyl ester.

1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic++ + acid methyl 1-(phenylmethyl)-3-piperidinyl ester 1, a highly potent calcium antagonist, was separated into stereo- and optical isomers to investigate the differences of antihypertensive activities between them. Fractional crystallization of the hydrochlorides of 1 gave alpha- and beta-diastereoisomers. The alpha-isomer (benidipine hydrochloride, KW-3049) showed very strong hypotensive effect, but little activity was observed in the beta-isomer. From optically resolved 1,4-dihydro-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-3- pyridinecarboxylic acids 2, and 1-benzyl-3-piperidinols 3, four optical isomers of 1 were synthesized, and their absolute configurations were deduced. The hypotensive activity of (+)-alpha, namely (S)-(S)-1, was 30 to 100 times stronger than that of (-)-alpha in intravenously administered spontaneously hypertensive rats.

Animals↗

PubMed1988

Synthesis of expected metabolites of benidipine hydrochloride.

(+/-)-(R*)-2,6-Dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3, 5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049, 1), a highly potent and long-acting calcium antagonistic 1,4-dihydropyridine derivative, is now under clinical study as an antihypertensive and as an antianginal agent. In order to confirm the structures of the metabolites of KW-3049, 19 compounds were prepared. Among them 11 compounds were found to be metabolites (the compounds 2, 3, 6, 8, 14, 15, 16, 28, 31, 32 and 34) of KW-3049 in rats and/or dogs.

Antihypertensive Agents↗

PubMed1988

Physico-chemical properties and stabilities of the highly potent calcium antagonist benidipine hydrochloride.

(+/-)-(R*)-2,6-Dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3, 5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049), a highly potent calcium antagonist, was examined to clarify its physico-chemical properties, i.e. melting point, spectra (UV, IR, NMR, MS), X-ray diffraction pattern, thermal analysis, solubilities, pKá, partition coefficient and chromatography (TLC, HPLC). The stabilities of KW-3049 were studied under various conditions by HPLC. KW-3049 in solid state was very stable to heat and moisture, and fairly stable to light.

Antihypertensive Agents↗

PubMed1988

Slow dissociation of the new slow-onset and long-acting calcium antagonist benidipine hydrochloride from 3H-nitrendipine binding sites.

The dissociation rates of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarb oxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) and some calcium antagonists from 3H-nitrendipine binding sites were studied by a centrifugation technique and a filter-absorbed tissue method. KW-3049 dissociated from 3H-nitrendipine binding sites more slowly than other calcium antagonist, namely nifedipine, nitrendipine, nilvadipine, nicardipine and nisoldipine. The slow dissociation of KW-3049 from 3H-nitrendipine binding sites was supported by the equilibrium binding studies. When KW-3049 was preincubated with rat cardiac membrane, its inhibitory potency was enhanced 2.6-fold, whereas nifedipine did not alter its potency. In ex vivo binding, following administration of KW-3049 to rat, 3H-nitrendipine binding site was occupied in a dose-dependent manner and this occupation returned to a control level after 24 h. These results of receptor binding studies are in agreement with the pharmacological characteristics of KW-3049.

Animals↗

PubMed1988

Antihypertensive effects of intravenous administration of benidipine hydrochloride and some other calcium antagonists in conscious, spontaneously hypertensive rats.

The antihypertensive effect of intravenously administered (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarb oxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) was examined in conscious, spontaneously hypertensive rats (SHR) and comparatively evaluated with those of nifedipine, nicardipine, nitrendipine, nisoldipine, verapamil and diltiazem. When nifedipine (10 and 100 micrograms/kg), nicardipine (10 and 100 micrograms/kg), nitrendipine (10 and 100 micrograms/kg), verapamil (100 and 1000 micrograms/kg) and diltiazem (100 and 1000 micrograms/kg) were intravenously administered to SHR, at their lower doses, only transient decreases of blood pressure were observed and, even at their higher doses, decreased blood pressures returned to the initial levels after 80 to 120 min. Nisoldipine at 10 micrograms/kg (i.v.) decreased the blood pressure (by 23 mmHg), lasting for 100 to 120 min, and the antihypertensive effect of 100 micrograms/kg (i.v.) of it (by 63 mmHg) lasted for longer than 240 min though a tendency of blood pressure to recover was observed. The peak effects of these 6 calcium antagonists were observed 1 min after the drug injection. When KW-3049 (1, 3, 10 and 30 micrograms/kg i.v.) was administered, a dose-dependent decrease of blood pressure (by 23 to 67 mmHg) was observed. The effect of KW-3049 was longer than those of the above 6 calcium antagonists, including nisoldipine. The maximal effects were attained 10 to 30 min after the drug injection and the decreased blood pressure did not return to an initial level even 180 min (at 1 and 3 micrograms/kg) and 240 min (at 10 and 30 micrograms/kg) after administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Antihypertensive effects of the new calcium antagonist benidipine hydrochloride in conscious, renal-hypertensive dogs.

The antihypertensive action of (+/-)-(R*)-2,6-dimethyl-4- (m-nitrophenyl)- 1,4-dihydropyridine-3,5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) was evaluated in conscious, renal-hypertensive dogs. When KW-3049 (0.1, 0.3 and 1 mg/kg) was orally administered, antihypertensive action and increased heart rate with peak time after 60 to 120 min of administration were observed, and the duration of actions at the dose of 0.3 mg/kg (p.o.) or more lasted for more than 7 h. When nifedipine (0.3 and 1 mg/kg) and nicardipine (1 and 3 mg/kg) were orally given, the duration of antihypertensive action was shorter. Nitrendipine (1 and 3 mg/kg p.o.) showed antihypertensive action and increased heart rate with peak time after 45 to 60 min of administration, and the duration of action at 3 mg/kg (p.o.) lasted for 7 h or longer. The antihypertensive activity of KW-3049 at the action peak was 6.1, 12.1 and 8.9 fold as compared with those of nifedipine, nicardipine and nitrendipine, respectively. Also, when KW-3049 at 0.3 mg/kg (p.o.) was administered after 1 h of propranolol (20 mg/kg p.o.) administration, the increase of the heart rate was markedly inhibited while its antihypertensive action remained unchanged. From these results, it was demonstrated that KW-3049 shows potent and long-lasting antihypertensive action with gradual appearance of action, and was suggested that it may be an useful antihypertensive agent.

Animals↗

PubMed1988

Effects of benidipine hydrochloride on atrioventricular conduction time and postural reflex in gallamine-immobilized cats.

Using gallamine-immobilized cats, the effect of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dic arb oxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) was compared with those of other drugs in terms of the propensity for atrioventricular conduction disturbances and orthostatic hypotension. The administration of KW-3049 at doses of 1 to 300 micrograms/kg i.v. dose-dependently lowered the blood pressure and also reduced the heart rate. In terms of the maximum blood pressure lowering activity, KW-3049 was similar in degree to nifedipine and approximately 30 times as potent as diltiazem, verapamil and phenoxybenzamine. KW-3049 as well as nifedipine, at doses with which the mean blood pressure can be reduced by 50 mmHg, hardly affected the PR-interval of ECG, whereas diltiazem and verapamil at their hypotensive doses markedly prolonged the PR interval. These four calcium antagonists at their high doses elicited 2nd or 3rd degree atrioventricular blocks in some cases. On the other hand, phenoxybenzamine did not affect the atrioventricular conduction at its hypotensive doses. Inhibitory action on the pressor responses to head-up tilting in cats was observed neither in KW-3049, nifedipine, verapamil nor diltiazem. On the contrary, phenoxybenzamine strongly inhibited the orthostatic pressor reflexes. From these results, it was suggested that in terms of the prolongation action of atrioventricular conduction KW-3049 is less potent than diltiazem and verapamil but similar in degree to nifedipine, and that KW-3049 is not likely to cause orthostatic hypotension.

Animals↗

PubMed1988

Antianginal effects of the new calcium antagonist benidipine hydrochloride in anesthetized rats and spontaneously hypertensive rats. Electrocardiographic study.

Antianginal effects of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)- 1,4-dihydropyridine-3,5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) in various experimental angina-pectoris models (anesthetized rats, spontaneously hypertensive rats (SHR] were compared with those of nifedipine, propranolol and hydralazine. Furthermore, the effects of these drugs on the pressure-rate product were evaluated. 1. Vasopressin test (SHR): The administration of KW-3049 at 10 micrograms/kg (i.v.) developed an inhibitory effect comparable to that of nifedipine at 200 micrograms/kg (i.v.) against the ischemic ECG changes caused by the intravenous administration of vasopressin at 1 U/kg. The effects of KW-3049 at 3 and 10 mg/kg (p.o.) lasted for 8 h or more. 2. Coronary occlusion test (rat): The rise of T-wave of epicardial ECG following ligation of coronary artery was inhibited by the administration of KW-3049 at doses of 30 and 100 micrograms/kg i.v. Nifedipine at dose of 200 micrograms/kg i.v. was slightly effective. 3. Isoproterenol (isoprenaline) test (rat): The fall of ST in ECG by the continuous infusion of isoprenaline (10 micrograms/kg/min) was almost completely prevented by propranolol (500 micrograms/kg i.v.). Also, KW-3049 (200 micrograms/kg i.v.) and nifedipine (200 micrograms/kg i.v.) significantly inhibited the decline of ST, in which the former was more effective than the latter. 4. Anoxia test (SHR): The fall of ST and rise of T-wave of ECG, induced by stopping artificial respiration of gallamine-immobilized SHR, were suppressed by the administration of KW-3049 at doses of 10 and 30 micrograms/kg i.v.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

PubMed1988

Vasodilating effects of the new calcium antagonist benidipine hydrochloride in anesthetized dogs and cats.

Vasodilating effects of a new 1,4-dihydropyridine derivative, (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3, 5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) were investigated in anesthetized dogs and cats. Intravenous administrations of KW-3049 at doses of 0.3 to 10 micrograms/kg exhibited a greater vasodilation in vertebral and coronary arteries than in common carotid and femoral arteries. The maximal effects of KW-3049 were equal to or more potent than those of nifedipine and nicardipine. Vertebral and coronary vasodilation following intravenous administration of 10 micrograms/kg of KW-3049 continued for 240 min or more, whereas those following nifedipine or nicardipine (10 micrograms/kg i.v.) disappeared within 30 min. A gradual and long-lasting increase of the vertebral and coronary blood flows following the intraduodenal administration of KW-3049 (0.1 mg/kg) was observed as compared with those of nifedipine (0.3 mg/kg i.d.) and nicardipine (0.3 mg/kg i.d.). When KW-3049 at a dose of 0.1 micrograms/kg was intraarterially administered to vertebral or coronary arteries, the blood flow increased without affecting systemic blood pressure and its effects lasted longer than those of nifedipine and nicardipine (0.1 micrograms/kg i.a.). In particular, the duration time in increase of coronary blood flow by KW-3049 was extremely longer, i.e. 11-fold and 6-fold those by nifedipine and nicardipine, respectively. Coronary vasodilating effect of KW-3049 was influenced neither by propranolol, atropine, diphenhydramine nor by aminophylline. Moreover, KW-3049 did not affect the vasodilator effect of adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗