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Biomedical subjects

A Akashi

Publications and source records attributed to A Akashi.

At least 91 records · Page 5Linked to original sources
PubMed1984

[A comparison of the effects of baclofen and some other muscle relaxants on alpha-rigidity in rats].

Muscle relaxant effects of baclofen were compared with those of dantrolene, diazepam, chlordiazepoxide and tolperisone. When administered intraduodenally (i.d.), baclofen and dantrolene but not diazepam suppressed the sustained rigidity of forelimbs in anemically decerebrated rats, and ED50 values of the former two drugs were 2.9 and 22 mg/kg, respectively. Baclofen, dantrolene and diazepam reduced the phasic rigidity of the decerebrated animals induced by mechanical stimulation of hindlimbs, with their respective ED50 values of 6.2, 140 and 1.4 mg/kg, i.d. Both the rigidities were almost insensitive to chlordiazepoxide and tolperisone. With the exception of tolperisone, these drugs also produced a muscle relaxation in intact animals as measured by traction (rats), rotarod (mice), and grip-strength (mice) tests. ED50 or eD25 values were calculated to be in the following ranges: 5.6 approximately 12 mg/kg, p.o. for baclofen, 15 approximately 35 mg/kg, p.o. for dantrolene, 2.1 approximately 6.5 mg/kg, p.o. for diazepam and 33 approximately 64 mg/kg, p.o. for chlordiazepoxide. These results suggest that baclofen, unlike other drugs, may be effective in reducing both tonic and phasic rigidities at lower doses than those causing muscle relaxation in intact animals.

Animals↗
PubMed1983

Characterization of the vasodilator action of antihypertensive drug budralazine.

Intravenous injection of 1-[2-(1,3-dimethyl-2-butenylidene)hydrazino]phthalazine (budralazine) to anesthetized dogs resulted in an increase in cardiac output and regional blood flow in various vascular beds, and a fall in mean blood pressure with a decreased total and regional vascular resistance. Budralazine produced a dose-related increase in femoral blood flow in anesthetized dogs when injected into the femoral artery. The vasodilator drug relaxed either KCl(K+)- or noradrenaline (NA)-induced contractions of isolated rabbit aorta in a concentration-dependent manner. In the K+-depolarized aorta, it also produced a concentration-related inhibition of contractile response to cumulative addition of Ca2+. Intra-arterial injection of budralazine dilated dose-dependently the isolated perfused vascular bed of rabbit ear constricted by either K+ or NA. Budralazine, at effective antihypertensive oral dose, was without significant effect on cyclic nucleotide levels in the aorta of spontaneously hypertensive rats (SHR). These results indicate that budralazine, like hydralazine, produces vasodilation through a direct effect on vascular smooth muscle which may result at least in part from its inhibitory effect on vascular Ca2+ fluxes.

Anesthesia↗
PubMed1981

Pharmacological studies on timiperone, a new neuroleptic drug Part II: General pharmacological properties.

General pharmacological properties of 4'-fluoro-4-[4-(2-thioxo-1-benzimidazolinyl) piperidino] butyrophenone (timiperone), a new neuroleptic drug, were compared with those of haloperidol. 1. Central nervous system: In behavioral observation, timiperone showed a typical neuroleptic profile at doses of 0.1 mg/kg p.o. and more (mice). The drug produced a moderate hypothermia at 10 mg/kg p.o. (rabbits), a mild increase in pain threshold at 3 mg/kg p.o. (mice and rats) and a slowing of cortical EEG at 1 mg/kg i.v. (cats). ED50 values of drug for the potentiation of ether and alcohol anesthesia were 0.34 and 0.22 mg/kg p.o., respectively (mice). Timiperone ahd neither an anticonvulsant activity at 30 mg/kg p.o. (mice) nor an effect on the spinal reflex at 1 mg/kg i.v. (cats). These effects of timiperone on the central nervous system were almost similar to those of haloperidol. 2. Respiratory and cardiovascular system: At dose of 0.03 mg/kg i.v. and more, timiperone produced transient increases in respiratory rate and regional arterial blood flow which were accompanied by a fall in blood pressure (dogs). Haloperidol had qualitatively similar effect, but was weaker than timiperone. Both drugs at high concentration (3X10-6 g/ml) exerted negative inotropic and chronotropic effect in isolated atrial preparations (guinea-pigs), and non-competitively antagonized the positive chronotropic action of isoprenaline. Atropine (2.5X10-7 g/ml) failed to modify the chronotropic action of timiperone (3X10-6 g/ml). 3. Autonomic nervous system: Timiperone at 0.1 mg/kg p.o. and haloperidol at 0.3 mg/kg p.o. induced a moderate miosis (rabbits) and antagonized blood responses to noradrenaline and acetylcholine (dogs). Both drugs at 1 mg/kg i.v. had no ganglion-blocking activity (cats). 4. Smooth muscle: In isolated guinea-pig ileum and vas deferens, timiperone and haloperidol (10-5 g/ml) antagonized the contractile responses of the muscles to various spasmogens, Both drugs at approximately 10-6 g/ml decreased spontaneous motility of the isolated rat uterus and inhibited the gastric secretion at 1 mg/kg i.p. (rats). At high doses, both drugs inhibited the gastrointestinal propulsion (mice), motility (dogs) and gastric emptying rate (rats), and had no damaging effect on the gastric mucosa (rats). 5. Skeletal muscle: At 0.1 mg/kg i.v., timiperone and haloperidol slightly enhanced twitch response of the anterior tibial muscle to electrical stimulation (rabbits). 6. Urine volume and urinary electrolytes: Timiperone and haloperidol showed a diuretic effect at 3 mg/kg p.o. whereas they inhibited urine output and electrolytes excretion at 30 mg/kg p.o. (rats).

Animals↗
PubMed1981

Pre- and postsynaptic alpha-adrenergic effects of the antihypertensive drug budralazine.

Cardiac presynaptic and vascular postsynaptic alpha-adrenergic effects of 1-[2-(1,3-dimethyl-2-butenylidene)hydrazino]phthalazine (budralazine) were studied in comparison with those of hydralazine. Budralazine was about 3 times less potent than hydralazine in producing tachycardia in spontaneously hypertensive and normotensive rats when compared at equihypotensive doses. In normotensive pithed rats, budralazine at 3 mg/kg i.v. affected neither the tachycardiac response to cardioaccelerator nerve stimulation nor the inhibition of clonidine of the stimulation-induced tachycardia. As the dose was increased to 6 and 12 mg/kg i.v., however, budralazine not only inhibited transiently the sympathetic tachycardia but also enhanced the clonidine bradycardia, although this drug was almost without effect on resting heart rate. These effects of budralazine on the heart rate response in the stimulated rats were partially but significantly antagonized by pretreatment with phentolamine. Hydralazine (3 mg/kg i.v.) differed from budralazine in that its transient inhibition of the stimulation-induced tachycardia was not modified by phentolamine and it produced an acceleration of the recovery of clonidine bradycardia as well as an increase in resting heart rate. Budralazine (3--12 mg/kg i.v.), like hydralazine (0.3 and 3 mg/kg i.v.), antagonized pressor responses to noradrenaline and phenylephrine but did not affect the tachycardia produced by both agonists in normotensive pithed rats. Based on these results, a possible mechanism of hypotensive and weak tachycardiac actions of budralazine is discussed in relation to that of hydralazine.

Animals↗
PubMed1981

Antihypertensive and general pharmacological properties of budralazine.

Antihypertensive and general pharmacological properties of 1-[2-(1,3-dimethyl-2-butenylidene)hydrazino]phthalazine (budralazine) were studied in comparison with those of hydralazine. Single oral administration of budralazine (4--15 mg/kg) to DOCA/saline hypertensive rats resulted in a dose-related and sustained antihypertensive effect which was 2--3 times less potent than that of hydralazine. However, there were no remarkable differences between both drugs in the hypotensive magnitude after the 4-week treatment of spontaneously hypertensive rats (SHR) with their higher doses. After single oral administration, budralazine was about 8 times less potent than hydralazine in increasing plasma renin activity in normotensive rats. At effective antihypertensive doses, budralazine inhibited spontaneous motor activity (mice), gastrointestinal propulsion (mice), gastric emptying rate (rats), gastric secretion (rats), urine output and urinary electrolyte excretion (rats) as well as carrageenan-induced paw edema formation (rats), which were essentially less potent than those produced by hydralazine. Budralazine at 6 mg/kg i.v. exhibited a slowing of neocortical EEG (cats) and a slight increase in spinal monosynaptic potentials (cats) and inhibited gastrointestinal motility (dogs). The same dose of hydralazine produced an increase in occurrence of the neocortical fast waves, an inhibition of the monosynaptic potentials and the carotid sinus reflex (dogs) and a stimulation of intestinal motility followed by prolonged and marked reduction. Budralazine (10(-5) g/ml) slightly potentiated contractile response of isolated guinea-pig vas deferens to noradrenaline, whereas hydralazine (10(-4) g/ml) inhibited the response. Budralazine (10(-5) g/ml), like hydralazine (10(-4) g/ml), produced a nonspecific antagonism against the contractile response of isolated guinea-pig ileum to various spasmogens, and both drugs (10(-4) g/ml) reduced either spontaneous motility or oxytocin-induced motility in isolated rat uterus.

Animals↗
PubMed1980

Interaction of cinepazide with adenosine on guinea-pig atria.

The negative inotropic effects of adenosine and adenine nucleotides, such as ATP and cAMP, on guinea-pig atria were selectively and dose-dependently augmented by cinepazide in concentrations insufficient to produce any effect alone (3 X 10(-5) M-3 X 10(-4)M). Adenosine (10(-5) M, 10 microCi) was degraded to inosine and hypoxanthine during incubation with atrial tissue. Cinepazide (3 X 10(-4) M) retarded the degradation of adenosine, and the formation of inosine and hypoxanthine. Incubation of the atrial tissue with adenosine (8.1 X 10(-9) M, 0.1 microCi) resulted in accumulation of 3H-activity. Cinepazide (3 X 10(-5) M-3 X 10(-4) M) inhibited this accumulation. These results suggest that cinepazide potentiates the negative inotropic effect of adenosine on guinea-pig atria by preventing both its degradation by deaminase and its accumulation by atrial tissue.

Adenosine↗
PubMed1979

[Cardiovascular pharmacology of cinepazide, a new cerebral vasodilator (author's transl)].

Cardiovascular effects of cinepazide were compared with those of cinnarizine and papaverine. Cinepazide (3-30 mg/kg, i.v.) produced a dose-related and transient increase in vertebral, carotid, renal and femoral arterial flow as well as cardiac output and a decrease in total peripheral resistance in anesthetized dogs. The magnitude and duration of mesenteric vasodilatation induced by cinepazide was much greater as compared to other vascular effects, and these effects were associated with a prolonged hypotension. The drug exerted positive inotropic and chronotropic actions, the latter being followed by bradycardia with the highest dose. Cinnarizine (0.3-3 mg/kg, i.v.) produced a greater increase in vertebral blood flow with bradycardia and papaverine (0.1-1 mg/kg, i.v.) produced a remarkable carotid vasodilatation with cardiac stimulation. Both reference drugs decreased renal blood flow. Cinepazide (30 mg/kg, i.v.) potentiated the vertebral vasodilator response of dogs to intravertebral adenosine and cyclic AMP, while cinnarizine (3 mg/kg i.v.) reduced their vasodilator effects. Intravertebral cinepazide(1-10 mg), like cinnarizine (0.1-1 mg) and papaverine (0.1-1 mg), increased vertebral blood flow in a dose-related manner and the effect was partially inhibited by intravenous pretreatment with aminophylline but not by pretreatment with autonomic antagonists. These antagonists did not modify the cinnarizine effect. Cinepazide resembled cinnarizine and papaverine in that the drug antagonized rabbit aortic contraction induced by KCl, norepinephrine or CaCl2.

Animals↗
PubMed1978

Pharmacology of budralazine, a new antihypertensive drug.

Antihypertensive and pharmacological properties of budralazine were examined in comparison with other antihypertensive drugs. Budralazine was orally effective against various types of hypertension in rats and it, like reserpine but unlike hydralazine, produced a much greater pressure reduction in hypertensive than in normotensive rats. The drug was similar to reserpine and alpha-methyldopa but not to hydralazine in showing a gradually progressive action. At equihypotensive oral doses, budralazine was less potent than hydralazine in producing tachycardia in unrestrained SHR. After long-term therapy, it effectively prevented the development of hypertension in SHR to almost the same extent as did hydralazine. Budralazine failed to produce diuresis in SHR at antihypertensive doses but antagonized isolated rabbit aortic contractions induced by vasoconstrictors and decreased femoral arterial resistance in dogs. Thus, the antihypertensive budralazine is characterized by the ability to produce vasodilator, non-diuretic and weak cardiac stimulant effects.

Animals↗
PubMed1976

[Pharmacological properties of lopramine].

Pharmacological properties of LOP were compared with those of imipramine(IMP). LOP had little or no effect on electroconvulsive shock and chemoconvulsions in mice, conditioned avoidance response in rats, pain threshold in mice and rats and body temperature in rabbits. LOP, unlike IMP, showed relatively weak effects on general behavior in mice, spontaneous EEG in cats and spontaneous motor activity in mice. LOP prevented oxotremorine-induced hypothermia but not tremor, while IMP antagonized both the responses in mice. In anesthetized dogs, LOP caused a respiratory stimulation and a fall in blood pressure, left ventribular pressure and left ventricular dp/dt without a noticeable effect on heart rate. LOP was less potent than IMP in the depressor and cardiodepressing effects, antispasmogenic activity and in antagonizing the depressor response to acetylcholine. LOP, like IMP, potentiated pressor response to norepinephrine and reduced that to tyramine in anesthetized dogs, but neither antidepressant produced norepinephrine potentiation in isolated guinea-pig vas deferens. Both drugs inhibited spontaneous motility of the jejunum without reducing the gastric motility in anesthetized dogs. These results indicate that, compared with IMP, LOP is characterized by weak general pharmacological activities.

Analgesics↗