PubMed Health⌕ Search

Biomedical subjects

L Pichler

Publications and source records attributed to L Pichler.

At least 55 records · Page 3Linked to original sources
PubMed1981

Modulation of motor activity by alpha 1- and alpha 2-adrenoceptor stimulation in mice.

The influence of two alpha-adrenoceptor agonists, clonidine and B-HT 920, on motor activity was tested in mice. Both, clonidine and B-HT 920 (2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo-[4,5-d]-azepine) in the dose range 30--300 micrograms/kg s.c. effectively inhibited exploratory activity. On the other hand only clonidine, which stimulates alpha 2- and alpha 1-adrenoceptors increased locomotor activity in mice treated with reserpine (5 mg/kg) and apomorphine (3 mg/kg) in the doses of 0.3 and 1 mg/kg i.p. The highly selective alpha 2-agonist B-HT 920 was ineffective under these conditions up to 30 mg/kg i.p. It is concluded, that in mice "sedative" alpha-adrenoceptors are of the alpha 2- and "excitatory" of the alpha 1-type.

Adrenergic alpha-Agonists↗
PubMed1980

Binding of an imidazolidine (clonidine), an oxazoloazepin (B-HT 933) and a thiazoloazepin (B-HT 920) to rat brain alpha-adrenoceptors and relation to cardiovascular effects.

The specific binding to alpha-adrenoceptors in crude plasma membrane preparations of the rat brain was studied by means of 3H-clonidine (specific radioactivity 26.7 Ci/mmole). Equilibrium binding of 3H-clonidine could be described adequately according to a two-site model with a minor population of high affinity sites (KD1 = 0.4 nM) and a major population of low affinity sites (KD2 = 6.1 nM). The heterogeneity of 3H-clonidine binding was also indicated by a biphasic association rate in kinetic binding studies. In competition experiments with 3H-clonidine concentrations of 0.5 or 4.0 nM respectively, concentration-dependent displacement was observed with the non-radioactive compounds: clonidine, B-HT 920 (2-amino-6-allyl-5, 6, 7, 8-tetrahydro-4H-thiazolo-[5, 4-d]-azepin-dehydrochloride) and B-HT 933 (2-amino-6-ethyl-4, 5, 7, 8-tetrahydro-6H-oxazolo-[5, 4-d]-azepin-dihydrochloride). IC50 values of 3, 21 and 160 nM or 10, 63 and 380 nM respectively were thereby evaluated. Cardiovascular effects were estimated in rats. The blood pressure increase in spinal animals was taken as parameter for alpha-adrenoceptor stimulation at peripheral vascular sites. The bradycardic effect in vagotomized animals was taken as parameter for central nervous sympathoinhibition. The ranking order of the potency of the three drugs was the same in both in vivo tests and parallels the in vitro binding affinities at both binding sites: clonidine greater than B-HT 920 greater than B-HT 933. These results indicate the similarity of the alpha-adrenoceptor structures in brain membrane preparations, at peripheral vascular sites and at central sympathoinhibitory sites.

Animals↗
PubMed1980

Relation between central sympathoinhibitory and peripheral pre- and postsynaptic alpha-adrenoceptors as evaluated by different clonidine-like substances in rats.

A series of 8 clonidine-like substances were tested in rats on central sympathoinhibition (heart rate decrease in vagotomized rats, D50 = dose which decreased heart rate by 50 beats/min), peripheral postsynaptic activity (blood pressure increase in spinal rats, PD30 = dose which increased blood pressure 30 mm Hg) and peripheral presynaptic activity (inhibition of tachycardia as elicited by electrical stimulation in the spinal canal of pithed rats, ID50 = dose which inhibited for 50%). The D50, PD30 and ID50 were converted in moles/kg and the negative logarithms thereof were correlated. There was a good correlation between the central effect (D50) and both peripheral effects (PD30 and ID50, respectively; r = 0.89 and 0.91, respectively) provided one drug with low lipoid affinity was omitted from calculation (St 600). There was also good correlation between both peripheral effects (PD30 and ID50; r = 0.94) and this could be extended to other imidazolines which are not acting centrally as antihypertensives (oxymetazoline, naphazoline, St 91, tramazoline; r = 0.90). The results were interpreted by (1) the agonistic activity of the clonidine-like drugs mainly at alpha 2-adrenoceptors and (2) the presence of alpha 2-adrenoceptors at peripheral presynaptic, peripheral postsynaptic as well as central cardiovascular sites.

Adrenergic alpha-Agonists↗
PubMed1980

Chemistry, pharmacology, and structure-activity relationships with a new type of imidazolines exerting a specific bradycardic action at a cardiac site.

The reaction of alkyl halides with 2-(arylimino)imidazolidines (I) leads to imidazoline derivatives II, in which the side chain is situated at the bridge nitrogen atom between the phenyl group and the imidazoline ring. The new imidazolines (II) exert a specific bradycardic action at a cardiac site. Syntheses and pharmacology are shown and structure-activity relationships discussed. The results reveal that the imidazoline derivatives (II) represent a class of compounds with a novel type of cardiac action.

Animals↗
PubMed1980

Central cardiovascular alpha-adrenoceptors. Relation to peripheral receptors.

Clonidine and related drugs cause a specific pattern of cardiovascular depression by an agonistic effect on alpha-adrenoceptors within the central nervous system (CNS). For further characterization of the central adrenoceptors, the actions of three substances of the "clonidine-type" derived from two different chemical groups were studied at peripheral vascular sites. Clonidine and two azepin derivatives had very weak vasoconstrictor activity in isolated perfused rat hindquarters. Signs of desensitization were observed when these drugs were administered repeatedly. However, these compounds exerted antagonism against the vasoconstricting effect of noradrenaline. The ranking order of these drugs in their antagonistic potency was the same as with their central cardiovascular depressor potency. In spinal rats, the three compounds raised blood pressure due to their alpha-adrenoceptor stimulation. The ranking order was the same for the pressor potency as for their central cardiovascular depressor potency. It is concluded that in isolated preparations the agonistic activity of clonidine-like substances on postsynaptic alpha-adrenoceptors might not be representative for their CNS effect.

Animals↗
PubMed1978

Differentiation of drugs acting centrally upon the cardiovascular system by means of sympathetic and vagal responses.

The response pattern of the autonomic nervous system was investigated after central administration (intra-cisternal, vertebral artery) of amphetamine, morphine, fentanyl, dextromoramide and the substance R 28935, chemically related to the neuroleptic agent pimozide. Effects on the sympathetic system were measured by recording electrical discharges of fibres of the (preganglionic) major splanchnic nerve in anaesthetized cats; those on the vagal system by recording the heart rate in anaesthetized dogs under beta-adrenoceptor blockade; the baroreceptor reflex was elicited by the blood pressure increase of i.v. injected angiotensin. All substances decreased the spontaneous discharge rate of the splanchnic nerve. Amphetamine facilitated the vagally mediated reflex bradycardia and this was antagonized by the alpha-adrenoceptor blocking agent piperoxan. Amphetamine did not affect the resting heart rate, as has already been shown for clonidine and related substances. The narcotic analgesics lowered the resting heart rate but did not facilitate the baroreceptor reflex response. R 28935 neither influenced resting heart rate nor the baroreceptor reflex response in beta-blocked dogs. On the basis of the vagal response pattern it was therefore possible to distinguish between 3 groups of central hypotensive drugs.

Amphetamine↗
PubMed1976

Centrally induced reduction in sympathetic tone-a postsynaptic alpha-adrenoceptor-stimulating action of imidazolines.

Naphazoline or oxymetazoline (both 30 mug/kg) were injected into the cisterna magna of anaesthetized cats and reduced blood pressure, heart rate and the electrical discharge rate of small fibre bundles of the preganglionic sympathetic splanchnic nerve. Cats were depleted of endogenous noradrenaline by pretreatment with reserpine (5 mg/kg, 18 h) and alpha-methyl-p-tyrosine (twice 300 mg/kg, 18 and 2 h). In these animals, intracisternal injection of 30 mug/kg oxymetazoline exerted a decrease of sympathetic discharges similar to that described for non-pretreated animals. In noradrenaline-depleted cats intracisternal injection of 1 mug/kg clonidine also decreased the sympathetic discharges. It is concluded that these imidazolines exert their sympathoinhibitory and cardiovascular effects by stimulation of postsynaptic alpha-adrenoceptors in the CNS.

Adrenergic alpha-Agonists↗
PubMed1975

Investigation into some imidazoline compounds, with respect to peripheral alpha-adrenoceptor stimulation and depression of cardiovascular centers.

Peripheral alpha-adrenoceptor stimulation was tested by means of hypertensive effects of the drugs following i.v. injection in spinal rats. Naphazoline (NP), oxymetazoline (OM), St 91-2-(2,6-diethylphenylimino)-2-imidazolidine--and St 1697--2-(2-ethyl, 6-methylphenylimino)-2-imidazolidine--were 3 to 5 times more potent in tthis respect thatn clonidine (CLON) whereas St 363--2-(2,4-dichlorophenylimino)-2-imidazolidine--and xylazine (XY) exerted only approx. 1/20 the effect of that of clonidine. Sympathoinhibitory activity after i.v. injection was tested by the bradycardiac effect in vagotomized rats; St 1697, St 363 and XY were active, approx. 1/10-1/30 of CLON, whereas NP, OM and St 91 were inactive. However, following intracisternal (i.ci.) injection of cardiovascular depression, typical for clonidine: (1) in dogs with blocked beta-adrenoceptors, the drugs facilitated the vagally meditated cardiodepressor reflex in response to baroreceptor stimulation by i.v. injection of angiotensin; (2) in dogs treated with atropine and in (3) vagotomized cats (only NP, OM and St 363) a long lasting decrease in heart rate was observed. Some of the experiments were complicated by increases in blood pressure, due to the "leakage" of small amounts of the highly vasopressor active drugs, from the cisternal spaces into the peripheral circulation. The majority of results indicated, that the central cardiovascular depressor effects of the tested drugs depend on their alpha-adrenoreceptor stimulating potency and on their ability to penetrate from cerebrospinal fluid or from the blood to cardiovascular centers. Relationships between the ability for penetration and the lipoid affinity are discussed.

Adrenergic alpha-Agonists↗
PubMed1975

Localization in the CNA of adrenoceptors which facilitate a cardioinhibitory reflex.

In dogs (pentobarbitone, 25 mg/kg) the brain was removed rostrally to the pons, leaving the cerebellum intact (decerebrate animals). In other animals the cerebellum was additionally removed (bulbar animals). In all animals beta-adrenoceptors were blocked by toliprolol (5 mg/kg s.c.). Angiotensin (0.025-0.3mug/kg) was repeatedly injected i.v. and the resulting maximal reflex bradycardia was recorded. Intracisternal (i.ci.) injection of clonidine, 0.5 to 1 mug/kg, in decerebrate or i.v. injection of 10 or 30 mug/kg in bulbar animals significantly facilitated the reflex bradycardia. This effect was antagonised by a subsequent injection of piperoxan 50 mug/kg i.ci. in decerebrate or 1 mg/kg i.v. in bulbar animals. It is concluded that the facilitatory action of clonidine is mediated by alpha-adrenoceptors within the medulla oblongata.

Adrenergic beta-Antagonists↗
PubMed1975

The central modulatory effect of clonidine on the cardiodepressor reflex after suppression of synthesis and storage of noradrenaline.

Rats were decerebrated and treated with a beta-adrenoceptor blocker (toliprolol, Kö 592, 5 mg/kg). Increases of blood pressure were repeatedly elicited by i.v. injection of angiotensin (0.03-0. 125 mug/kg) ant eh accompanying reflex bradycardia was measured. The vagally mediated reflex bradycardia was significantly increased by clonidine, 3o mug/kg i.v., in non-pretreated animals as well as after pretreatment with reserpine (7.5 mg/kg s.c., 20 hr) and alpha-methyl-p-tyrosine-methylester (250 mg/kg i.p., 5 hr), separately or in combination. The facilitatory effect of clonidine was antagonized in all groups by i.v. injection of the alpha-adrenoceptor blocking drugs, phentolamine (5 mg/kg) and piperoxan (1 mg/kg). In the control periods before clonidine, reflex bradycardia was similar in pretreated animals to that in animals without pretreatment. It was concluded therefore that catecholamines have no essential transmitter functions in the cardiodepressor reflex loop. Therefore, the action of clonidine on cardiovascular centers in the medulla is independent of endogenous noradrenaline storage and synthesis. A direct effect is assumed on central alpha-adrenoceptors, which have a modulatory 'effector' function on the cardiodepressor reflex.

Adrenergic beta-Antagonists↗