Interchangeability evaluation of multisource Ibuprofen drug products using biowaiver procedure.

The WHO biowaiver procedure for BCS Class II weak acids was evaluated by running two multisource IR ibuprofen drug products (Ibuprofen, 200 mg tablets, Tatchempharmpreparaty, Russia and Ibuprofen, 200 mg tablets, Biosintez, Russia) with current Marketing Authorizations (i.e. in vivo bioequivalent) through that procedure. Risks associated with excipients interaction and therapeutic index were considered to be not critical. In vitro dissolution kinetic studies were carried out according WHO Guidance (WHO Technical Report Series, No. 937, Annexes 7 and 8) using USP Apparatus II (paddle method) at 75 rpm. Dissolution profiles of test and reference ibuprofen tablets were considered equivalent in pH 4.5 using factors f(1) (13) and f(2) (72) and not equivalent in pH 6.8 (factor f(1) was 26 and f(2) was 24). Drug release of ibuprofen at pH 1.2 was negligible due to its weak acid properties. Therefore, two in vivo bioequivalent tablets were declared bioinequivalent by this procedure, indicating that procedure seems to be over-discriminatory.

[Omeprazol and ezomeprazol pharmacokinetics, duration of antisecretory effect, and reasons for their probable changes in duodenal ulcer].

There were authentic distinctions between the groups of healthy volunteers and patients with a peptic ulcer disease in Cmax, Tmax, AUC(0-t), AUC(0-infinity), CIt, Vd of omeprazole and Cmax of esomeprazole (Nexium, AstraZeneca). When the pharmacokinetics of omeprazole and ezomeprazole were compared in both groups, there were authentic distinctions in Cmax, AU(0-t), AUC(0-infinity), CIt, T1/2. The patients who had taken omeprazole the time of hypoacide condition was much shorter than in other groups. Disintegration test modeling pHmax for pH oscillation with large amplitude, that is typical for ulcer disease, demonstrated a possibility of early partial release of omeprazole, its acid-depended degradation and reduction of its bioavailability.

[The effect of pharmacopuncture on the blood biochemical indices of patients with tunnel syndromes of the hands]. / Vliianie farmakopunktury na biokhimicheskie pokazateli krovi bol'nykh s tunnel'nymi sindromami ruk.

Concentrations of serotonin, beta-endorphine, myoglobin, basic myelin protein were measured in blood of patients with tunnel hand syndromes treated by actovegin or physiological solution pharmacopuncture and acupuncture to the same acupuncture points (AP). The above biochemical indices showed similar changes in pharmacopuncture with actovegin and the solution. These changes were different in acupuncture. This indicates specificity of AP stimulation by introduction of fluid, but not specificity of drug effects.

[The effect of scalp acupuncture on the blood biochemical indices of healthy volunteers]. / Vliianie skal'popunktury na biokhimicheskie pokazateli krovi zdorovykh dobrovol'tsev.

Scalp acupuncture effects on blood biochemistry were investigated in 10 healthy volunteers. The results provided evidence for the absence of negative changes in function of neurohumoral systems of the body which may become factors of risk for patients with thrombogenic disturbances of cerebral circulation.

[The role of group-A10 dopamine neurons of the ventral tegmental area in analgesia evoked by electrocutaneous pain stimulation and morphine]. / Rol' dofaminovykh neironov gruppy A10 ventral'noi tegmental'noi oblasti pri obezbolivanii, vyzvannom élektrokozhnym bolevym razdrazheniem i morfinom.

The activity of antinociceptive mechanisms induced by footshock (FS) and morphine injection was studied in experiments on rats with bilateral destruction of group A10 neurones of the ventral tegmental area. The latent periods of the hot plate and tail flick pain reactions to FS and morphine increased significantly in the experimental and control groups as compared to the initial values. In morphine injection these indices were the same in the experimental and control groups. In FS the latent periods of the reaction were significantly greater in the experimental group. Thus, destruction of dopaminergic neurons of A10 nuclei intensifies the antinociceptive effects in FS but has no effect on the pain-relieving action of systemic morphine injection.

[Changes in pain reactions and 3H-naloxone binding to opiate receptors of the hypothalamus and midbrain in rats after repeated swimming in cold water]. / Izmenenie bolevykh reaktsii i sviazyvaniia 3H-naloksona s opiatnymi retseptorami gipotalamusa i srednego mozga krys posle mnogokratnogo plavaniia v kholodnoi vode.

The dynamics of nociceptive reactions and character of 3H-naloxone binding to hypothalamus and midbrain synaptic membranes were studied in rats subjected to repeated cold swim stress (3 min. daily during 3, 5 and 15 days). It was shown that an increase of latencies of background nociceptive reactions (hot-plate and tail-flick tests) was accompanied by an ambiguous changes of kinetic parameters of 3H-naloxone binding in the studied brain structures. The results suggest that an increase of antinociceptive systems tone under repeated cold swim stress may be caused by a dynamic transformation of opiate u-receptor apparatus in various brain structures.

[Effect of amitriptyline on analgesia induced by acupuncture and inescapable painful electrodermal stimulation in the rat]. / Vliianie amitriptilina na obezbolivanie, vyzvannoe akupunkturoi i neizbegaemym bolevym élektrokozhnymrazdrazheniem u krys.

The effect of amitriptyline (1.5 and 3 mg/kg intraperitoneally once a day for 1, 3, 5 days) on the latencies (L) of hot plate (HP) and tail flick (TF) at rest, after acupuncture (A) of bilateral Ho-ku and after inescapable foot-shock (IFS--1.0 mA, 50 Hz, 5 min) was studied in experiments on rats. It was shown that amitriptyline in the above doses, used in different periods of time, failed to effect L of HP and TF at rest. However, after A an increase of the analgesic effect was observed in the rats treated with 3 mg/kg of amitriptyline for 3 days. In the experiment with IFS an increase of the effect was pronounced in TF test 24 hours following administration of 1.5 and 3.0 mg/kg of amitriptyline.

[The role of catecholaminergic group-A5 neurons in analgesia induced by auricular electroacupuncture and in electrodermal pain stimulation]. / Rol' katekholaminergicheskikh neironov gruppy A5 pri obezbolivanii, vyzvannom aurikuliarnoi élektroakupunkturoi i élektrokozhnym bolevym razdrazheniem.

The activity of antinociceptive mechanisms of auricular electroacupuncture (AEA) and footshock (FS) was studied on rats with bilaterally lesioned group A5 neurones. It was shown that the activity of the antinociceptive mechanisms triggered in experimental rats as compared to control rats. The data reveal the involvement of A5-nuclei in the antinociceptive mechanisms of AEA and FS.

Buspirone effect on the development of antinociceptive reactions.

The anxiolytic agents, buspirone and diazepam, increase the paw lick latency of rats in the hot plate test, the effect being dose-dependent and exceeding that of morphine. The action of buspirone was not accompanied by ataxic and sedative effects which were observed in rats on diazepam. Buspirone (up to 25 mg/kg) and diazepam (up to 5 mg/kg) neither change the tail flick latency nor potentiate the action of morphine on the test. A buspirone dose of 2 mg/kg administered to animals before foot shock, or the dose of 1.5 mg/kg before cold swimming stress, led to a significant increase in hot plate latency 1 min after stress as compared to the control. The effect of buspirone on the paw lick reaction in rats may be related to the activation of antinociceptive mechanisms and inhibition of an emotional-motivational component of the pain reaction.

[The role of group A5 catecholaminergic neurons in stress and morphine analgesia mechanisms in rats]. / Rol' katekholaminergicheskikh neironov gruppy A5 v mekhanizmakh stressovoi i morfinnoi anal'gezii u krys.

The activity of antinociceptive mechanisms in cold stress and under the effect of morphine was studied in experiments on rats subjected to bilateral destruction of group A5 neurons. In cold stress in rats of the experimental and control groups the latent periods (LP) of pain reactions of limb licking differed significantly, both in initial values and between the groups; in contrast, the LP of the tail-flick reaction did not differ significantly. Under the effect of morphine the pain reactions increased authentically as compared to the initial values both in the experimental and the control groups, but there were no significant differences between the groups. Thus, group A5 noradrenergic neurons have an effect on inhibiting some pain reaction components in cold stress, but are of no importance in the mechanisms of antinociceptive actions under the effect of morphine.

[Effects of repeated acupuncture action on pain sensitivity and beta-endorphin contents of the hypothalamus and midbrain of the rat]. / Vliianie mnogokratnogo akupunkturnogo vozdeistviia na bolevuiu chuvstvitel'nost' i soderzhanie beta-éndorfina v gipotalamuse i srednem mozge krys.

Changes in latencies (L) of nociceptive (NC) reactions of hot plate (HP) tail flick (TF) tests and dynamics of beta-endorphin (beta-ED) in hypothalamus and midbrain were studied in albino rats receiving 15 sessions of acupuncture (A) (20 min daily in bilateral Ho-Ku). It was shown that repeated A facilitated prolongation of LHP and LTF as compared to baseline and control levels. A decrease of the anti-NC systems capacity for activation in response to each A stimulation was observed. The dynamics of beta-endorphin in hypothalamus showed an opposite tendency as compared to that in midbrain. It is suggested that such a correlation of beta-ED activities in midbrain and hypothalamus might be one of the reasons for anti-NC mechanisms adaptation to A.

[The selective role of the nucleus raphe magnus in the mechanisms of analgesia in electrocutaneous pain stimulation, cold stress and the action of morphine]. / Izbiratel'naia rol' bol'shogo iadra shva v mekhanizmakh obezbolivaniia pri élektrokozhnom bolevom razdrazhenii, kholodovom stresse i deistvii morfina.

Inhibition of the analgetic activity of systemic morphine and inescapable foot shock in certain moments of the experiment was shown on rats subjected to electrolytic destruction of nucleus raphe magnus. Cold swim stress increased analgesia as compared to the control animals. It is concluded that this formation of the brain is selectively and dynamically involved in mechanisms of various types of analgesia.

[Role of giant cell nuclei of the reticular formation in mechanisms of analgesia during auricular electroacupuncture and action of morphine]. / Rol' gigantokletochnykh iader retikuliarnoi formatsii v mekhanizmakh obezbolivaniia pri aurikuliarnoi élektroakupunkture i deistvii morfina.

The activity of antinociceptive mechanisms induced by auricular electroacupuncture (AEA) and intraperitoneal injection of morphine (M) was studied on rats subjected to bilateral lesion of gigantocellular nuclei (GCN). It was shown that under AEA hot-plate (HP) and tail-flick (TF) latencies (L) significantly increased as compared to the baseline level. A comparison of L shows that HP and TF in the experimental group were significantly shorter than in the control group. After M injection the rats of both the experimental and control groups showed a significant increase of HP L and TF L as compared to the baseline level, but there was no difference in L between the groups. It is concluded that neurochemical systems of GCN are involved in the mechanism of antinociception elicited in AEA while the mechanisms of antinociceptive effect of M do not involve GCN.

[Role of the locus coeruleus in the mechanism of different types of analgesia]. / Rol' sinego piatna v mekhanizmakh raznykh vidov obezbolivaniia.

The activity of antinociceptive mechanisms during exposure to cold swim stress (CSS), inescapable foot shock (FS) and morphine administration (10 mg/kg) was studied in rats subjected to bilateral lesions of locus coeruleus (LC). It has been shown that under all types of stimulation the latent periods (LP) of nociceptive reactions of paw licking and tail flick were significantly increased, as compared to baseline level, thus suggesting suppression of the pain sensitivity. In rats subjected to CSS and morphine administration significantly shorter LP were revealed in the experimental group, compared to the control, which suggested partial inhibition of antinociceptive mechanisms activity after LC lesion. FS did not cause any differences in the experimental and control groups. It is concluded that LC lesions cannot completely inhibit the antinociceptive mechanisms activated by CSS and morphine injection. In FS monoamine mechanisms of LC do not seem to play an important role in the functioning of antinociceptive mechanisms.

[Analysis of the influence of anxiolytics on the pain reactions of rats compared to the effect of morphine]. / Analiz vliianiia anksiolitikov na bolevye reaktsii u krys v sravnenii s éffektom morfina.

Anxiolytic agents, buspirone and diazepam, increase the paw lick latency of rats in hot plate test, the effect being dose-dependent and exceeding that of morphine. The action of buspirone was not accompanied by ataxic and sedative effects which were observed in rats on diazepam. Buspirone (up to 25 mg/kg) and diazepam (up to 5 mg/kg) neither change the tail flick latency nor potentiate the action of morphine in this test. The effect of buspirone on the paw lick reaction in rats may be related to the inhibition of emotional-motivation component of pain reaction.

[Features of the cytoarchitectonics of the periaqueductal gray of the cat midbrain]. / Osobennosti tsitoarkhitektoniki okolovodoprovodnogo serogo veshchestva srednego mozga koshki.

When studying cytoarchitectonics of the midbrain periaqueductal gray (PAG) in cat four areas were distinguished: medial, dorsal, lateral rostral and lateral caudal. They differ in size and distribution density of neurons.

Cortical projections to the periaqueductal grey in the cat: a retrograde horseradish peroxidase study.

Stereotaxic fluid microinjections of horseradish peroxidase into different parts of the rostral and caudal periaqueductal grey (PAG) in cats have provided substantial retrograde evidence that the somatosensory cortex (I and II), frontal cortex, insular and cingular cortex are the principal sources of cortical-PAG projections. The somatosensory cortex II projects to all the regions of the rostral and caudal PAG. The frontal cortex projects to dorso-lateral quadrant of the PAG. The same projections were determined from insular and cingular cortex to PAG. The findings revealed a morphological substratum of corticofugal effects on PAG.