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Biomedical subjects

V Klimek

Publications and source records attributed to V Klimek.

At least 55 records · Page 3Linked to original sources
PubMed1985

Adaptive and differential changes on beta- and alpha 2-adrenoreceptors mediated hyperthermia after chronic treatment with antidepressant drugs in the rat kept at high ambient temperature.

We found previously that the beta-agonist clenbuterol and the alpha-agonist clonidine produced hyperthermia in rats kept at high ambient temperature, which effects were mediated by beta- and alpha 2-adrenoceptors, respectively. In the present paper this observation was used for testing the responsiveness of beta- or alpha 2-adrenoceptors, changed by a pharmacological manipulation, i.e., by chronic treatment with antidepressants. The animals were pretreated with desipramine, imipramine or amitriptyline twice a day for 1 or 2 weeks. All antidepressants significantly attenuated the clenbuterol-induced hyperthermia after 2 weeks of treatment. The effect of desipramine was stronger than that of the other antidepressants and appeared as little as 1 week after the treatment. The hyperthermic effect of clonidine was significantly reduced by repeated treatment with desipramine, increased after 2 weeks administration of imipramine, whereas amitriptyline produced no significant changes. In conclusion, these data suggest that, after repeated treatment, the antidepressants tested produce an adaptive decrease in function of beta-adrenoceptors while the same drugs exert differential effects on alpha 2-receptors. Moreover, clenbuterol induced hyperthermia may be a useful test for examining possible functional changes in beta-adrenoceptor sensitivity.

Amitriptyline↗
PubMed1984

Distinct target size of dopamine D-1 and D-2 receptors in rat striatum.

Frozen rat striatal tissue was exposed to 10 MeV electrons from a linear accelerator. Based on the theory of target size analysis, the molecular weights of dopamine D-1 receptors (labelled by 3H-piflutixol) and dopamine D-2 receptors (labelled by 3H-spiroperidol) were 79,500 daltons and 136,700 daltons, respectively. The size of the dopamine-stimulated adenylate cyclase was 202,000 daltons. The estimated molecular sizes were deduced by reference to proteins with known molecular weights which were irradiated in parallel. The results showed that the molecular entities for 3H-piflutixol binding and 3H-spiroperidol binding were not identical. The present results do not allow conclusions as to whether D-1 and D-2 receptors are two distinct proteins in the membrane, or whether the receptors are located on the same protein. In the latter case the binding of 3H-spiroperidol needs the presence of a second molecule.

Adenylyl Cyclases↗
PubMed1981

Chronic treatment with antidepressants: protentiation of clonidine-induced aggression in mice via noradrenergic mechanism.

The chronic (10 mg/kg i.p. twice daily, 10 days)-and not the acute-administration of amitriptyline, maprotiline or zimelidine enhances aggressiveness induced by clonidine in mice. An analogous potentiation of clonidine-induced aggressiveness was obtained with chronic administration (the schedule as above) of levomepromazine (2 mg/kg) or thioridazine (5 mg/kg) but not of spiperone (0.2 mg/kg). Fluoxetine (10 mg/kg), atropine (5 mg/kg), propranolol (10 mg/kg) or metergoline (0.5 mg/kg) given chronically (the schedule as above) also had no effect. The enhancement of clonidine aggressiveness induced by prolonged treatment with imipramine (10 mg/kg) was prevented by cycloheximide, an inhibitor of protein synthesis. The results supply further evidence for the previously proposed hypothesis that chronic administration of antidepressants enhances the responsiveness of central postsynaptic noradrenaline receptors.

Aggression↗
PubMed1979

The effect of repeated administration of antidepressant drugs on the responsiveness of rats to catecholamine agonists.

The antidepressant drugs, imipramine (10 mg/kg s.c.), amitriptyline (10 mg/kg s.c.), mianserin (2 mg/kg i.p.), danitracen (3 mg/kg i.p.) or the vehicle were administered to rats twice a day for 4 or 10 days. Clonidine (0.5 mg/kg s.c.) induced in rats chronically treated with the compounds studied an increase in locomotor activity but, at the same time, did not affect or decreased this activity in rats chronically treated with the vehicle or a single dose of an antidepressant. This refers, in particular, to imipramine, amitriptyline and danitracen which have a similar effect. This effect, an increase in motility, was most pronounced and common for all the three drugs (after a 4- and 10-day treatment) when clonidine was administered 72 hours after the last dose of an antidepressant. Only in a few cases the amphetamine-induced hypermotility was enhanced by a chronic administration of antidepressants (a 4-day amitriptyline treatment, 72 hours after the last injection; a 4-day mianserin or danitracen treatment, 48 hours after the last injection). The results obtained seem to suggest that a chronic administration of the antidepressant drugs may cause a change in the sensitivity of the central noradrenaline receptors.

Amitriptyline↗
PubMed1977

Effect of nomifensine on central 5-hydroxytryptamine neurons.

Effects of nomifensine (8-amino-1, 2, 3, 4-tetrahydro-2-methyl-4-phenyl-isoquinoline) (NF), an antidepressant drug which inhibits dopamine uptake, on central serotonergic structures were studied in rats. NF affects of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid levels in the whole brain as well as in the separate rat brain structures. The 5-HT turnover is decreased in the whole brain and the striatum but increased in the midbrain and the hippocamp as judged from experiments with tryptophan hydroxylase inhibitor, alpha-propyldopacetamide. Pretreatment with dopamine-receptor blocking agent, spiperone, antagonized the increase of 5-HT turnover rate in brain regions mentioned above. NF stimulates the hind limb flexor reflex in spinal rat, a preparation regarded as a model for evaluation of drug action on central 5-HT neurons. This stimulatory effect was antogonized by cyproheptadine, by reserpine and imipramine. The obtained results indicate that NF activates central 5-HT neurons both directly and indirectly, via stimulation of dopamine receptors as described previously for other dopamine agonists.

Animals↗
PubMed1977

Drugs affecting dopamine neurons and yawning behavior.

Drugs stimulating the dopamine (DA) neurons in different ways (apomorphine, piribedil, amphetamine, nomifensine, L-DOPA) given in low doses (not producing behavioral excitation) induced yawning in rats. Blockade of DA receptors with neuroleptics counteracted DA-agonists induced yawning which may indicate a dopaminergic component of this behavior.

Adrenocorticotropic Hormone↗
PubMed1976

On the anticataleptic action of cyproheptadine.

The anticataleptic action of cyproheptadine, a tricyclic compound known as antiserotonin, anticholinergic and antihistaminic drug in comparison to that of atropine, promethazine, imipramine, desipramine, chlorimipramine and nomifensine was studied in rats. The catalepsy induced by spiperon, pimozide or fluphenazine was antagonized by cyproheptadine, atropine and promethazine. Imipramine and nomifensine were less active, desipramine and chlorimipramine without effect. The reserpine- and alpha-methyltyrosine-catalepsy was counteracted by cyproheptadine, promethazine and nomifensine, but not by atropine or tricyclic antidepressants. Only cyproheptadine and promethazine antagonized the catalepsy caused by a combined treatment with reserpine and alpha-methyltyrosine. The pilocarpine-catalepsy was abolished by atropine, promethazine and nomifensine and unaffected by tricyclic antidepressants. Atropine and promethazine antagonized also the physostigmine-catalepsy. The catalepsy induced by both cholinomimetic drugs was not changed or increased by cyproheptadine. The results presented indicate that cyproheptadine differs in its anticataleptic activity from all the drugs used for comparison. Possible mechansims of this activity are discussed.

Animals↗
PubMedDate not supplied

Changes in the rat brain 5-HT1A and 5-HT2 receptors after chronic administration of levoprotiline, (+)-oxaprotiline and other antidepressant drugs.

The effects of levoprotiline (LEV), a (-)-enantiomer of oxaprotiline (OXA) and a clinically effective antidepressant, on the binding parameters of hippocampal 5-HT1A and cortical 5-HT2 receptors of rats were compared with those of (+)-enantiomer of OXA ((+)-OXA), imipramine and mianserin. Both LEV and (+)-OXA displayed in vitro some affinity for 5-HT1A receptors labelled with [3H]-8-OH-DPAT, and for 5-HT2 receptors labelled with [3H]-ketanserin. Repeated administration of LEV, for 14 days led to a marked increase in the number of 5-HT1A binding sites in the rat hippocampus, with no change in the KD values. (+)-OXA, imipramine and mianserin produced similar effects on 5-HT1A binding parameters. The number of 5-HT2 receptors was increased after two weeks of LEV administration, not altered after (+)-OXA, and decreased after imipramine or mianserin. The number of [3H]-ketanserin binding sites was decreased after four weeks of (+)-OXA administration, but not altered after LEV. The specific binding of [3H]-ketanserin in the rat cerebral cortex was decreased after repeated treatment with LEV and (+)-OXA (ex vivo). In competition studies the affinity of serotonin for [3H]-ketanserin binding sites was decreased in LEV- and increased in (+)-OXA-treated rats. The results suggest that LEV similarly to other antidepressants increases the number of 5-HT1A receptors, however without common alteration in 5-HT2 receptor number and function.

Animals↗
PubMedDate not supplied

The influence of antiserotonergic agents on the action of dopaminergic drugs.

The effect of drugs blocking serotonin receptors: cyproheptadine, methysergide, and methergoline, and of serotonin synthesis inhibitor, p-chlorophenylalanine on the stereotyped behavior and number of rearings of the rats receiving apomorphine, amphetamine, nomifensine and 1,3-dimethyl-5-aminoadamantane was investigated. The blockade of serotonin receptors potentiates behavioral effects of dopamine agonists. It is concluded that central serotonin may play an inhibitory role, antagonistic to that of catecholamines.

Animals↗
PubMedDate not supplied

Effect of chronic administration of antidepressant drugs on the noradrenaline disappearance induced by FLA-63 in the rat brain.

We evaluated noradrenaline (NA) level and NA disappearance after FLA-63 in some regions of the brain of rats chronically treated with antidepressants: imipramine (IMI), amitriptyline (AMI) and danitracen (DAN). IMI (10 mg/kg sc), AMI (10 mg/kg sc) and DAN (3 mg/kg ip) were administered to rats twice daily for 10 days. Experiments with a single dose of antidepressants were carried out for comparison. Given chronically, IMI decelerated NA disappearance in the cortex after 2, 24, 48 hr but accelerated it 72 hr after the last injection; AMI did not produce any change in the brain regions examined up to 72 hr; DAN accelerated NA disappearance in the cortex and in the limbic system, whereas it effected no changes in the pons+medulla. These results indicate that: 1) the effects of chronic administration of IMI, AMI or DAN on the brain NA disappearance are different, 2) chronic administration of antidepressants produces effects not found at a single administration.

Amitriptyline↗
PubMedDate not supplied

Antidepressants given repeatedly increase the alpha 1-adrenoceptor agonist affinity in the rat brain.

Several different antidepressant drugs (AD): imipramine, amitriptyline, citalopram and mianserin were administered to rats at a dose of 10 mg/kg po, twice daily for 14 days. The competition studies showed that AD used enhanced the ability of alpha 1-agonist phenylephrine to inhibit the binding of [3H]-prazosin to its receptors (Ki values being decreased) in the cerebral cortex, thalamus and hippocampus. The present results show that the increase in the affinity of alpha 1-adrenoceptors for their agonist is responsible for the functional alpha 1-adrenergic hypersensitivity found after repeated treatment with different AD.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

Central beta- and alpha-adrenolytic activities of adimolol.

The central adrenergic blocking activity of adimolol (ADL) was studied in rats and mice in the tests which can differentiate beta-, alpha 1-, and alpha 2-adrenolytic effects. Clenbuterol- and salbutamol-induced sedation in rats (open field test) and clenbuterol-induced hyperthermia (at high ambient temperature) were antagonized by low doses of ADL (0.1-1.0 mg/kg ip). ADL (10 mg/kg ip) attenuated the clonidine-induced aggression in mice, and its higher doses (20 and 40 mg/kg ip) depressed the hind limb flexor reflex of the spinal rat and counteracted the stimulatory action of clonidine. ADL at doses from 2.5 to 40 mg/kg ip affected neither the clonidine-induced sedation in rats and mice (locomotor activity, open field test), nor the hyperthermia (at high temperature). The hypothermia (at a room temperature of 21 degrees C) induced by clonidine was partially antagonized. The Ki values for ADL displacement of 3H-dihydroalprenolol and 3H-prazosin binding in the rat cerebral cortex were 1.2 nM and 951 nM respectively. These results indicate that ADL is a potent antagonist of central beta-adrenoceptors and has a weaker alpha 1-adrenolytic action. The central alpha 2-antagonistic effect is either very weak or absent.

Adrenergic alpha-Antagonists↗