PubMed Health⌕ Search

Biomedical subjects

D A Kharkevich

Publications and source records attributed to D A Kharkevich.

At least 19 recordsLinked to original sources
PubMed1999

Pharmacological regulation of descending cortical control of the nociceptive processing.

Clinical and experimental data indicate that the cerebral cortex plays an important role in pain perception and endogenous antinociceptive system function. Moreover, the enhancement of descending inhibitory cortical control may be involved in the mechanisms of analgetic effect of some agents. The present study was designed to investigate the effect of cortical electrical stimulation (as a model of descending inhibitory control) on the behavioral and electrophysiological signs of nociceptive response, decipher the mechanisms involved therein and evaluate the action of central analgesics (both opioid and non-opioid) on descending cortical control. In acute experiments in cats the inhibitory cortical influence on neuronal activity produced by nociceptive stimuli (electrical stimulation of tooth pulp, C-fibers of afferent somatic nerves, afferent cardiac structures) was most marked after stimulation of the first and second sensory and fronto-orbital areas. In chronic experiments on rats cortical stimulation reduced behavioral signs of visceral pain (writhing test) and also delayed the development of neuropathic pain syndrome along with lowering its intensity. Mu-opioid receptor agonists (morphine, fentanyl) potentiated the inhibitory cortical effect on the evoked neuronal activity. Pentazocine, which has pronounced kappa-receptor agonistic activity, was less effective. Naloxone eliminated the effects of both cortical stimulation and opioid analgesics. Serotonin receptor antagonist methysergide as well as p-chlorophenylalanine significantly decreased inhibitory cortical control and opioids effect. Monoamine re-uptake inhibitors with analgetic properties (imipramine, fluoxetine) potentiated the inhibitory effect of cortical stimulation. Adrenoceptor, dopamine, acetylcholine, GABA-receptor agents and antagonists of NMDA receptors had minor or no effect. Among non-narcotic analgesics, inhibitors of cyclooxygenase, metamysole and ketorolak increased only moderately the descending cortical control of nociception. Thus, the cerebral cortex is able to control the nociceptive processing in different pain syndromes (somatic, visceral or neuropathic pain). Opioidergic and serotonergic systems play the key role in this control. The effect over the cortical descending control is likely to be one of the components of the analgetic effect exerted by opioids and some other central analgesics.

Analgesics, Non-Narcotic↗
PubMed1998

[The descending cortical control of nociceptive signals: the neurochemical mechanisms and pharmacological control].

The purpose of the present study was to determine whether electrical cortical stimulation (as a model of descending inhibitory control) could alter the electrophysiological and behavioral signs of a nociceptive response. The inhibitory cortical influence on the neuronal activity produced by nociceptive stimuli (the tooth pulp, C-fibers of afferent somatic nerves, cardiac afferents) was most marked during electrical stimulation the somatosensory (Sn and St) and fronto-orbital cortices. In chronic experiments, somatosensory cortical stimulation delayed the development of the deafferentation pain syndrome and reduced its intensity. The opioid mu-receptor agonists morphine and fentanyl potentiated the inhibitory action of the cortex on evoked neuronal activity. Pentazocine, a kappa-receptor agonist, was less effective. The opioid receptor blocker naloxone eliminated the effect of both cortical stimulation and opioid analgesics. The serotonin receptor blocker methisergide significantly decreased cortical action. Monoamine reuptake inhibitors (amitriptyline, imipramine, fluoxetine) potentiated the effect of cortical stimulation. Adrenergic, dopaminergic cholinergic, and GABA-ergic substances had a little effect. Among nonopioid analgesics, metamyzol and ketorolak only increased moderately descending cortical control.

Animals↗
PubMed1997

Delivery of loperamide across the blood-brain barrier with polysorbate 80-coated polybutylcyanoacrylate nanoparticles.

PURPOSE: The possibility of using polysorbate 80-coated nanoparticles for the delivery of the water insoluble opioid agonist loperamide across the blood-brain barrier was investigated. The analgesic effect after i.v. injection of the preparations was used to indicate drug transport through this barrier. METHODS: Loperamide was incorporated into PBCA nanoparticles. Drug-containing nanoparticles were coated with polysorbate 80 and injected intravenously into mice. Analgesia was then measured by the tail-flick test. RESULTS: Intravenous injection of the particulate formulation resulted in a long and significant analgesic effect. A polysorbate 80 loperamide solution induced a much less pronounced and very short analgesia. Uncoated nanoparticles loaded with loperamide were unable to produce analgesia. CONCLUSIONS: Polysorbate 80-coated PBCA nanoparticles loaded with loperamide enabled the transport of loperamide to the brain.

Analgesics↗
PubMed1995

Passage of peptides through the blood-brain barrier with colloidal polymer particles (nanoparticles).

Transport of the hexapeptide dalargin across the blood-brain barrier was accomplished using a nanoparticle formulation. The formulation consisted of dalargin bound to poly(butyl cyanoacrylate) nanoparticles by sorption, coated with polysorbate 80. Intravenous injection of this formulation to mice resulted in an analgesic effect. All controls, including a simple mixture of the three components (drugs, nanoparticles, and surfactant) mixed directly before i.v. injection, exhibited no effect. Analgesia was also prevented by pretreatment with naloxone. Fluorescent and electron microscopic studies indicated that the passage of the particle-bound drug occurred by phagocytic uptake of the polysorbate 80-coated nanoparticles by the brain blood vessel endothelial cells.

Animals↗
PubMed1994

Opioid ligands with extraordinarily high mu-selectivity: dermorphin tetrapeptides containing thymine-modified alanine residues.

Four new [D-MetO2]dermorphin tetrapeptides with substituted N- and C-terminal groups and a thymine-modified alanine residue at position 4 were prepared and tested for their activity. All analogues were found to be mu-opioid receptor ligands. Two of them, H-Tyr-D-MetO-Phe-TalNHR (R = H, Ad) displayed an extremely high mu-opioid receptor selectivity comparable with that of the most mu-selective agonists among opioid peptides.

Alanine↗
PubMed1991

Stimulant effect of thyrotropin-releasing hormone and its analog, RGH 2202, on the diaphragm respiratory activity, and their antagonism with morphine: possible involvement of the N-methyl-D-aspartate receptors.

Thyrotropin-releasing hormone (TRH) was reported to stimulate respiration and abolish the respiratory depressant effect of morphine-like analgesics. Some TRH analogs which have a diminished hormonal activity may be of interest as potential non-specific opioid antagonists. The mechanism of this effect of TRH and its analogs is still unclear. Thus, in the present work the respiratory stimulant effect of TRH and its analog RGH 2202 was studied in the urethane-anesthetized vagotomized artificially-ventilated rats. The integrated diaphragmatic electromyogram was used to evaluate the effects of the drugs. TRH and RGH 2202 administered either i.v. or directly onto the dorsal medullary surface significantly increased the respiratory activity of the diaphragm. TRH and RGH 2202 also effectively antagonized the diaphragm activity depression caused by morphine. The latency, time course and activity of RGH 2202 turned out to be close to those of TRH. The possible involvement of N-methyl-D-aspartate (NMDA) receptors in the mechanism of action of TRH and RGH 2202 was also investigated. It was shown that the non-competitive NMDA antagonists ketamine and MK-801 and the competitive antagonist D-amino-5-phosphonovalerate after local or i.v. administration prevented or discontinued the diaphragm activity stimulation by TRH and RGH 2202. Moreover, they blocked the antagonistic action of TRH and RGH 2202 on the morphine-induced diaphragm activity depression. Thus, we conclude, that TRH and RGH 2202 cause similar stimulant effects on the respiratory activity of the diaphragm and effectively antagonize its depression by morphine. These effects are likely to be mediated by the NMDA receptors located in the central respiratory structures.

Animals↗
PubMed1990

Antinociceptive activity of muscarinomimetic agents.

The effect of the agents with muscarinomimetic activity on the nociceptive transmission in the spinal cord was studied in spinal rats. Oxotremorine (5-20 micrograms/kg, i.v.), arecoline (0.25-1.0 mg/kg, i.v.), pilocarpine (5-20 mg/kg, i.v.) and aceclidine (0.25-1.0 mg/kg, i.v.) inhibited the nociceptive flexor reflex induced by intraarterial injection of bradykinin. Muscarinomimetics in the same doses and anticholinesterase agents physostigmine (1-4 micrograms, intrathecally) and galanthamine (25-100 micrograms, intrathecally) inhibited bradykinin-induced bioelectric activity in the spinal ventrolateral tracts. Atropine (1 mg/kg, i.v.) abolished the inhibitory effect of the agents tested on the nociceptive flexor reflex and bioelectric activity.

Action Potentials↗
PubMed1989

Employment of magnet-susceptible microparticles for the targeting of drugs.

It has been demonstrated in cats that magnet-susceptible microspheres and liposomes containing neuromuscular blocking agents (dipyronium, pyrocurinum and diadonium) caused a deeper inhibition of the neuromuscular transmission in the limb placed in the magnetic field than in the control limb located beyond the field. The microparticles containing a short-acting neuromuscular blocking agent diadonium appeared to have the highest selectivity of action. The present method allows a pronounced neuromuscular block in a target area to be achieved without noticeable effect on PCO2 of the exhaled air.

Animals↗
PubMed1986

[Study of magnet-controlled transport of curare-like preparations of diadonium and dipyronium in animal experiments].

The experiments on cats have shown that liposomes containing ferrocolloid and neuromuscular blocking agents (diadonium or dipyronium) cause selective muscle relaxation in the animal limb placed into the magnetic field, compared to the control limb kept outside the field. This effect was not related to the action of the magnetic field per se on neuromuscular transmission or the potency of neuromuscular blocking agents not contained in liposomes, but was induced by the accumulation of magnet-controlled liposomes in the target limb. The use of magnet-controlled liposomes for diadonium and dipyronium transport to one of the animal limbs decreases their unfavourable effect on respiratory muscle function.

Adamantane↗
PubMed1981

The effect of neuromuscular blocking agents on the acetylcholine receptors of different skeletal muscles.

The comparative sensitivity of acetylcholine receptors of different skeletal muscles--m. masseter, m. gastrocnemius, m. triceps brachii, mm. obliquus et transversus abdominis, mm. intercostales, m. phrenicus to neuromuscular blocking agents was investigated. Experiments were performed on cats anesthetized with urethane (600 mg/kg, i.v.) and chloralose (70 mg/kg, i.v.). Muscle action potentials evoked by electrical stimulation of motor nerves were recorded. Derivatives of alpha-truxillic acid--anatruxonium and cyclobutonium, steroidal neuromuscular blocking agents--pancuronium and pipecurium, decamethonium and succinylcholine and their N-adamantyl analogues--decadonium and diadonium respectively, as well as tubocurarine chloride were tested. It was shown that the succession of relaxation of different skeletal muscles induced by the neuromuscular blocking agents of different chemical structure is variable.

Animals↗
PubMed1980

Cardiotropic antimuscarinic action of some curare-like agents.

In anesthetized cats antidepolarising curare-like drugs anatruxonium, cyclobutonium, diadonium and decadonium in doses lower than myoparalytic ones, completely blocked acetylcholine-induced bradycardia, only slightly changing the hypotensive action. In a myoparalytic dose anatruxonium and cyclobutonium decreased acetylcholine bronchospasm approximately by 50 %, diadonium altered this response in various directions, while decadonium essentially increased the bronchoconstricting action of acetylcholine. Anatuxonium and cyclobutonium failed to affect significantly the ileum, urinary bladder or salivary glands responses to acetylcholine; diadonium increased or did not change these reactions, while decadonium significantly enhanced them. Anatruxonium like atropine antagonized carbachol effects on isolated ileum and spontaneously beating atria of the rat, causing parallel shifts of the concentration-response curves for the agonist with no depression of maximum responses. Still, unlike atropine the affinity (pA2) of anatruxonium for muscarine-sensitive acetylcholine receptors of the atria was higher than that for the receptors of the ileum. The data obtained testify to the heterogenity of muscarine-sensitive acetylcholine receptors of different localisation.

Animals↗
PubMed1979

[Application of mechanotronic transducers in experimental biological investigations].

Mechanotronic transducers applied usually in technical investigations for the measurement of displacements, tensions, pressures and other mechanical parameters have been studied to register the contractile activity of isolated organs (the frog heart ventricle, the rat ileum strips) and the blood pressure in anesthetized animals. It was found that the mechanotronic transducers are simple, convenient and reliable devices for such investigations.

Animals↗