Epinephrine potentiates the analgesic and antidepressant effects of polyvinylpyrrolidone and cholecystokinin due to stimulation of afferents in the gastric mucosa

Treatment with epinephrine, polyvinylpyrrolidone, and cholecystokinin in the minimum effective doses produced maximum analgesic and antidepressant effects and caused bradycardia in rats. Administration of epinephrine in combination with polyvinylpyrrolidone or cholecystokinin in threshold doses (1/10–1/25 of the minimum effective dose) produced maximum analgesic and antidepressant effects, but did not cause bradycardia. The potentiating effect of epinephrine is related to stimulation of afferents in the gastric mucosa. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 3, pp. 321–323, March, 2007     

Epinephrine potentiates antipsychotic,but not cataleptogenic effect of haloperidol in rats

Intramuscular injection of haloperidol or epinephrine in a minimum effective dose produces the maximum antipsychotic effect in rat model of schizophrenia, i.e. completely removes stereotypy, hyperlocomotion, and ataxia induced by MK-801. Haloperidol in the specified dose induces catalepsy, while epinephrine exhibits no cataleptogenic effect. Combined intramuscular injection of haloperidol and epinephrine in the threshold doses, ineffective in monotherapy, causes the maximum antipsychotic effect, but not catalepsy. Preliminary anesthesia of the gastric mucosa with 1% lidocaine and blockade of intramural ganglia in the gastric mucosa with hexamethonium completely abolished the potentiated antipsychotic effects produced by combined treatment with haloperidol and epinephrine. Hence, potentiation of the antipsychotic effect of haloperidol with epinephrine is related to stimulation of afferents in the gastric mucosa. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 5, pp. 554–556, May, 2007     

Involvement of central and peripheral cannabionoid receptors in the regulation of heart resistance to arrhythmogenic effects of epinephrine

Intravenous injection of the selective cannabinoid receptor agonist HU-210 in doses of 0.05 and 0.25 mg/kg increased heart resistance to arrhythmogenic effects of epinephrine, while intracerebroventricular infusion of this substance had no effect on the incidence of epinephrine-induced arrhythmia. The selective antagonist of type I cannabinoid receptors SR141716A in a dose of 3 mg/kg and ganglion blocker hexamethonium in a dose of 10 mg/kg did not modify the antiarrhythmic effect of HU-210. This effect of HU-210 is probably related to activation of type II peripheral cannabinoid receptors. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 130, No. 11, pp. 552–554, November, 2000     

Involvement of the serotoninergic system in the mechanism of action of ultralow dose antibodies to S-100 protein

The involvement of the serotoninergic system in the realization of anxiolytic and anti-depressant activities of antibodies to S-100 protein in ultralow doses is proven. Administration of ultralow-dose antibodies to S-100 protein in combination with serotoninergic agents (ketanserin and 5-hydroxytryptophan) reduced the anxiolytic and antidepressant effects of antibodies. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 5, pp. 535–537, May, 2007     

Comparative study of analgesic potency of ACTH<Subscript>4–10</Subscript> fragment and its analog semax

The effects of ACTH_4–10 fragment and its analog semax on nociception were examined on various animal models. ACTH_4–10 in a dose of 0.5 mg/kg decreased nociception in rats during hindpaw compression test and in mice subjected to acetic acid writhing test. Lower doses of ACTH_4–10 produced no analgesic effect. Semax (0.015–0.500 mg/kg) decreased pain sensitivity in all experimental models. Hence, the substitution of three C-terminal amino acid residues in ACTH_4–10 for Pro-Gly-Pro sequence augmented the analgesic potency of the peptide after its peripheral injection. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 1, pp. 8–12, January, 2007     

Anxiolytic and antidepressant characteristics of impaza

Antibodies to endothelial NO synthase in ultralow doses exhibited anxiolytic and antidepressant effects and their efficiency after single and course treatment is not inferior to that of amitriptyline and diazepam. The psychotropic activity of ultralow-dose antibodies to endothelial NO-synthase is presumably one of important mechanisms of their efficiency in the treatment of erectile dysfunction. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 145, No. 6, pp. 682–684, June, 2008     

Analgesic effect of corticotropin-releasing hormone: Involvement of the hypothalamic-pituitary-adrenocortical axis into its realization

Involvement of hypothalamic-pituitary-adrenocortical axis into the analgesic effect of corticotropin-releasing hormone after its systemic administration was studied in experiments on rats. Pharmacological blockade of the hypothalamic-pituitary-adrenocortical axis decreased the duration and degree of the analgesic effect of corticotropin-releasing hormone. This analgesic effect can be mediated via two pathways: related to hormones of the hypothalamic-pituitary-adrenocortical axis and independent of these hormones. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 2, pp. 144–146, February, 2006     

Hemodynamic effects of tetrindol in alert normotensive mice and rats after blockade of nitric oxide synthesis

Single intravenous injection of antidepressant tetrindol (1 and 10 mg/kg), a reversible monoamine oxidase A inhibitor, dose-dependently decreased heart rate and mean arterial pressure (in a concentration of 10 mg/kg) in alert NMRI mice and Sprague-Dawley rats. Nitric oxide synthase blockade with L-NAME attenuated tetrindol-induced bradycardia in rats and completely abolished this effect in mice. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 130, No. 8, pp. 193–195, August, 2000     

Involvement of the GABA-B system in the mechanism of action of ultralow-dose antibodies to S-100 protein

The involvement of the GABA-B neurotransmitter system in the realization of anxiolytic and antidepressant activities of ultralow-dose antibodies to S-100 protein is demonstrated. Simultaneous injection of ultralow-dose antibodies to S-100 protein and GABA-B receptor agonist baclofen reduced the anxiolytic and antidepressant effects of the drug, while GABA-B receptor antagonist faclofen stimulated the anxiolytic and reduced the antidepressant effect of ultralow-dose antibodies to S-100 protein. The effect of ultralow-dose antibodies to S-100 protein on the GABA-B-ergic system differs from that of benzodiazepine anxiolytics (diazepam) and tricyclic antidepressants (amitryptiline) not affecting this transmitter system. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 5, pp. 552–554, May, 2008     

Amitriptyline-induced ultrastructural changes in various structures of rat brain

The immediate effect of amitriptyline on various brain structures is characterized by the standard ultrastructural changes in neurons: emergence of numerous coated vesicles in the cytoplasm and formation of cisternae within a 3-h period. These changes are most pronounced in the sensorimotor cortex. Changes in the structure of cytoplasmic organelles are reversible; they disappear 24 h after administration of amitriptyline. Astrocytes respond to the preparation by activation of lysosomes, being the most sensitive cell type of the neuroglia. Numerous synaptic vesicles are seen in the axodendritic synapses. Newly formed fibers in the neuropile may be associated with the antidepressant effect of amitriptyline. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 10, pp. 457–461, October, 1996     

Effect of pectin substances on contractile activity of the uterine myometrium in rats

We studied the effects of peptides from Amaranthus cruentus L., Rauwolfia serpentina Benth., and citrus plants on contractile activity of the uterine myometrium in rats. Pectin substances inhibited spontaneous contractile activity of uterine muscles and abolished the stimulatory effect of oxytocin. Pectins had a synergistic effect with epinephrine and acetylcholine. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 4, pp. 414–417, April, 2006     

Effect of imipramine on the behavior and cerebral 5-HT1A serotonin receptors in mice genetically predisposed to catalepsy

Acute injection of imipramine to NPK mice hereditary predisposed to pinching catalepsy reduced immobility in the forced swimming test, but had no effect on catalepsy. Chronic treatment with imipramine reduced the severity of catalepsy and functional activity of 5-HT_1A serotonin receptors, but did not modify their expression in the hippocampus. NPK mice can be a convenient model for studies of the effects of antidepressant. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 1, pp. 53–55, January, 2006     

Effect of glibenclamide on antinociceptive effects of antidepressants of different classes

OBJECTIVES:

The purpose of this work was to determine whether the intraperitoneal administration of glibenclamide as a K_ATP channel blocker could have an effect on the antinociceptive effects of antidepressants with different mechanisms of action.

METHODS:

Three antidepressant drugs, amitriptyline as a dual-action, nonselective inhibitor of noradrenaline and a serotonin reuptake inhibitor, fluvoxamine as a selective serotonin reuptake inhibitor and maprotiline as a selective noradrenaline reuptake inhibitor, were selected, and the effect of glibenclamide on their antinociceptive activities was assessed in male Swiss mice (25-30 g) using a formalin test.

DISCUSSION:

None of the drugs affected acute nociceptive responses during the first phase. Amitriptyline (5, 10 mg/kg), maprotiline (10, 20 mg/kg) and fluvoxamine (20 and 30 mg/kg) effectively inhibited pain induction caused by the second phase of the formalin test. Glibenclamide (5 mg/kg) alone did not alter licking behaviors based on a comparison with the control group. However, the pretreatment of animals with glibenclamide (10 and 15 mg/kg) partially reversed the antinociceptive effects of fluvoxamine but not those of maprotiline. In addition, the highest dose of glibenclamide (15 mg/kg) partially prevented the analgesic effect of amitriptyline.

CONCLUSION:

Therefore, it seems that adenosine triphosphate-dependent potassium channels have a major role in the analgesic activity of amitriptyline and fluvoxamine.     

Combined blockade of α3β4 nicotinic acetylcholine receptors and GluR1 AMPA receptors in rats prevents kainate-induced tonic-clonic seizures

Intramuscular injection of IEM-1754, a blocker of cerebral GluR1 AMPA receptors, in doses of 0.5–3.0 mg/kg decreased the incidence of kainate-induced tonic-clonic seizures and mortality rate by 2.7–4 times. IEM-1678, an α3β4 nicotinic acetylcholine receptor antagonist administered intramuscularly in a maximum dose of 3 mg/kg decreased the incidence of kainate-induced tonic-clonic seizures and mortality rate by 2.3–2.7. IEM-1460 blocking both GluR1 AMPA receptors and α3β4 nicotinic acetylcholine receptors, injected intramuscularly in doses of 0.5–3.0 mg/kg produced the maximum anticonvulsant activity and 8-fold decreased the incidence of kainate-induced tonic-clonic seizures and mortality rate. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 5, pp. 548–550, May, 2007     

Antidepressant activity of β-lactam antibiotics and their effects on the severity of serotonin edema

Injection of β-lactam antibiotics (reterpen, ceftazidime, and thienam) to mice in doses equivalent to the mean therapeutic doses for humans led to shortening of the duration of behavioral despair in the hanging by the tail test, modified the resistance to serotonin edema, and intensified the exploratory and orientation activity in the open field test. This sum of effects was detected after 10 injections of retarpen and thienam and after single and five-fold administration of ceftazidime. Antidepressant sertraline also shortened the duration of behavioral despair and reduced serotonin edema. An inverse correlation between the duration of behavioral despair and severity of serotonin edema was detected in control mice. The results suggest that β-lactam antibiotics are characterized by antidepressant effect related to changes in serotonin sensitivity. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 7, pp. 82–85, July, 2006     

Histidine increases β-adrenoreactivity of myocardium in frogs

Histidine (3×10⁻⁵ g/ml) had no effect on contractility and chronoinotropic relationship in frog myocardium, but rapidly and reversibly increased myocardial β-adrenoreactivity (increased myocardial response to 7×10⁻⁸, 3×10⁻⁷, and 4×10⁻⁷ g/ml epinephrine) and potentiated the positive effect of epinephrine (7×10⁻⁸, 3×10⁻⁷ g/ml) on chronoinotropic relationships in the myocardium. Histidine is considered to be a component of endogenous sensitizer of β-adrenoceptors in human blood modulating the function of cardiomyocytes. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 8, pp. 144–147, August, 2004     

The role of central mechanisms in the anti-inflammatory effect of amitriptyline on carrageenan-induced paw edema in rats

OBJECTIVE:

The present study was designed to further investigate the effect of amitriptyline, a classical tricyclic antidepressant, on carrageenan-induced paw edema in rats.

METHODS:

First, amitriptyline was administered intraperitoneally (i.p.) at doses of 20, 40 and 80 mg kg^-1, 30 min before subplantar injection of carrageenan. Second, amitriptyline was given intracerebroventriculary or intrathecally at doses of 25, 50 and 100 µg/rat, 30 min prior to carrageenan challenge. Third, the effect of adrenergic receptor antagonists such as propranolol (10 mg kg^-1, i.p.), prazosin (4 mg kg^-1, i.p.) and yohimbine (10 mg kg^-1, i.p.) and an opioid receptor antagonist (naloxone, 4 mg kg^-1, i.p.) on the anti-inflammatory effect of amitriptyline (40 mg kg^-1, i.p.) was investigated.

RESULTS:

Our data confirm that intraperitoneally administered amitriptyline exhibits a marked anti-inflammatory effect on carrageenan-induced paw edema in rats 4 h postcarrageenan challenge (P < 0.001). Intracerebroventricular (i.c.v.) administration of amitriptyline also reduced the development of paw edema at 4 h postcarrageenan (P < 0.001), but intrathecal (i.t.) application of amitriptyline failed to alter the degree of paw swelling. Furthermore, the applied antagonists did not modify the anti-inflammatory effect of amitriptyline.

CONCLUSION:

These results support the view that amitriptyline has a considerable anti-inflammatory effect on carrageenan-induced paw edema in rats and suggest that at least a part of this property could be mediated through supraspinal sites. Moreover, it seems unlikely that the investigated adrenergic and opioid receptors have a significant role in this effect of amitriptyline.     

Changes in agent variability and time course of disease incidence during a year (as exemplified by dysentery)

The vulnerability of epidemic process during the period of minimum annual incidence of the disease is validated. Biological properties ofShigella sonnei are studied and their variability examined using the index for evaluation of the mean number of variations for a sign. Minimum agent heterogeneity coincides with minimum incidence of disease and maximum heterogeneity with its seasonal rises. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 130, No. 11, pp. 558–560, November, 2000     

The effects of serotonin/norepinephrine reuptake inhibitors and serotonin receptor agonist on morphine analgesia and tolerance in rats

Several studies have demonstrated that serotonergic and noradrenergic systems have important roles in morphine analgesia and tolerance. However, the exact mechanism underlying the development of morphine tolerance is not fully understood. The aim of this study was to investigate the possible role of serotonin/norepinephrine reuptake inhibitors (amitriptyline, venlafaxine) and serotonin receptor (5-HT(1A) and 5-HT(1B/1D)) agonist (dihydroergotamine) in morphine analgesia and tolerance in rats. To constitute morphine tolerance, animals received morphine (50 mg/kg; s.c.) once daily for 3 days. After the last dose of morphine was injected on day 4, morphine tolerance was evaluated. The analgesic effects of amitriptyline (20 mg/kg; i.p.), venlafaxine (20 mg/kg; s.c.), dihydroergotamine (100 μg/kg; i.v.) and morphine (5 mg/kg) were considered at 15- to 30-min intervals (0, 15, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests. In this study, the data obtained suggested that amitriptyline and venlafaxine significantly increased the analgesic effect of morphine and attenuated the expression of morphine tolerance. However, dihydroergotamine significantly increased the analgesic effect of morphine but did not reduce the expression of morphine tolerance. In conclusion, we determined that co-administration of morphine with amitriptyline and venlafaxine increased the analgesic effects of morphine and attenuated the morphine analgesic tolerance.