[Study of analgesic effect of novel imidazoline derivatives and their effect on arterial pressure during pain]. / Izuchenie boleutoliaiushchego deistviia novykh proizvodnykh imidazolina i ikh vliianiia na arterial'noe davlenie v usloviiakh bolevogo vozdeistviia.

In rat experiments new imidazoline derivatives caused a pain-relieving effect and inhibited a rise in arterial pressure in pain. Fluoride derivatives of imidazoline in doses of 1, 2, and 4 mg/kg induced long-term analgesia, had no effect on the background arterial blood pressure (AP), and significantly reduced its nociceptive pressor responses. The bromide derivatives of imidazoline showed no noticeable pain-relieving activity but reduced the nociceptive AP shifts. The background AP parameters did not change in this case. The prospects of directed chemical modification of imidazoline derivatives to obtain new analgesics capable of reducing the undesirable hemodynamic manifestations of pain are discussed.

[The potential antinarcotic effects of guanfacine]. / Potentsial'nye antinarkoticheskie éffekty guanfatsina.

alpha 2-Agonist clonidine has been used for several years in the detoxification of opiate-addicts since it reduces withdrawal symptoms in man although craving for narcotic is not well suppressed. In the present work the potential "anticraving" properties of another alpha 2-agonist guanfacine were studied in rats trained to self-administer morphine. In the special series of experiments the influence of guanfacine on behavioral manifestation of morphine withdrawal in rats was studied. Analgesic action of guanfacine was evaluated by tail-flick procedure. It was shown that guanfacine (2-4 mg/kg, i.p.) essentially inhibited the morphine intravenous self-administration in a dose-dependent manner. These findings can be interpreted as reduction of morphine's positive reinforcing properties by guanfacine and point out on the possibility to prevent morphine abuse by guanfacine. Analgesic effect of guanfacine in tail-flick test was revealed in doses of 1-8 mg/kg, i.p. (50-100% increase in latency of nociceptive reaction, p < 0.05, Student's t-test). In the other experiments the morphine dependence was induced by i.p. injections of this drug during 5 day period with gradually elevated doses from 5 up to 25 mg/kg. Morphine discontinuation and injection of naloxone (0.5 mg/kg, i.p.) on day 6 induced the behavioral symptoms of abstinence ("wet dog shakes" and jumping). Guanfacine (4 mg/kg, i.p., immediately after naloxone) significantly increased the number of jumps and locomotions (p < 0.05), while increase in "wet dog shakes" was not statistically significant. The potentiation of morphine-withdrawal jumping by guanfacine was antagonized by iohimbine and prazosine in doses of 1 mg/kg, i.p. In the same conditions both prazosine and iohimbine removed "wet dog shakes." The results suggest that the potentiation effect of guanfacine on morphine-withdrawal jumping in rats can be mediated through alpha 1- and alpha 2-adrenoreceptors. Nonspecific interaction between prazosine and mentioned effect of guanfacine (which can be resulted from potentiation of blood pressure fall and of motor deficit) cannot be excluded.

[The analgesic action of new enkephalin analogs]. / O boleutoliaiushchem deistvii novykh analogov énkefalinov.

The enkephalin analogue peptide IKB-901 containing epsilon-ACA and cysteine with the modified S-end shows an analgetic activity in rats (1 micron, intrathecally and 5 mg/kg intravenously) and in cats (0.35 and 0.7 mg/kg intravenously). Naloxone (0.1 mg/kg) prevents the analgetic effect of peptide. The coadministration of the peptide and the enkephalinase inhibitor D-phenylalanine (0.35 and 10 mg/kg, respectively) enhances analgesia and displays an antihypertensive effect in nociceptive stimulation.

[Neurophysiological mechanisms of the antihypertensive effect of clopheline in pain]. / Neirofiziologicheskie mekhanizmy antigipertenzivnogo éffekta klofelina pri boli.

In experiments on conscious and unanesthetized cats it was shown that clopheline in analgesic doses do not change the pain baroreflex blood pressure regulation and mild brain antinociceptive sympathoactivating influences. The clopheline antihypertensive effect was due to nonopiate direct sympathoinhibitory effect realized by suprasegmental level of vasomotor regulation.

[The effect of morphine and opiate receptor agonists on arterial pressure and the bioelectrical activity of the renal nerve during stimulation of the midbrain central gray substance]. / Vliianie morfina i agonistov opiatnykh retseptorov na arterial'noe davlenia i bioélektricheskuiu aktivnost' v pochechnom nerve pri razdrazhenii tsentral'nogo serogo veshchestva srednego mozga.

It has been demonstrated in experiments on unrestrained and unanesthetized curarized cats that periaqueductal gray matter stimulation produce sympathetic-activating action, raise arterial pressure and heart rate, but at the same time is not effective enough to suppress the nociceptive shifts of haemodynamic reactions. Opioid mechanisms of spinal cord plays an essential role in sympathetic-activating action of periaqueductal gray matter. It is suggested that the influence of antinociceptive areas of the brain stem on sympathetic haemodynamic regulation is one of the causes of resistance of nociceptive haemodynamic reactions to narcotic analgetics.

[Effect of morphine on the supra- and segmental mechanisms of regulating arterial pressure in pain]. / Vliianie morfina na supra- i segmentarnye mekhanizmy reguliatsii arterial'nogo davleniia pri boli.

It has been demonstrated in experiments on nonanesthetized intact and spinalized cats that intrathecal morphine increased blood pressure and renal nerve sympathetic activity and enhanced the nociceptive reactions. It is suggested that morphine plays an essential role in the effect of propriospinal system on the generation of sympathetic spinal reflexes.

[A computer system for the synchronous staged analysis of the indices of bioelectrical activity and systemic hemodynamics]. / Komp'iuternaia sistema dlia sinkhronnogo poétapnogo analiza pokazatelei bioélektricheskoi aktivnosti i sistemnoi gemodinamiki.

Programmes have been designed for computerized assessment of bioelectrical impulse amplitude, duration and frequency, simultaneously with instant indexes of systolic, diastolic arterial pressure and heart rate.