**Appendix**


**Drug Studied activity Test system Results Ref**

*Association between Peripheral Blood Inflammatory Markers, Endothelial Dysfunction Markers,…*

Adult Wistar male rats with hypoestrogeninduced NO deficiency

Hypertensive adult ISIAH male rats

Normotensive adult Wistar male rats

Thoracic aorta rings of adult male SHR

Adult outbred male rats with experimental acute hemic hypoxia

Brain cortex neurites of rat fetuses (gestational day 17) without any branching

rats with β-amyloidinduced amnesia

rats

Antidepressive activity Adult outbred male rats

*DOI: http://dx.doi.org/10.5772/intechopen.88693*

Anxiolytic activity Adult outbred male rats

Influence on the cardiovascular system

Divaza Endothelio-protective activity

> Neuroprotective (antioxidant) activity

Neurotropic activity (neurite outgrowth)

**115**

Anti-amnestic activity Adult Wistar male

Antidepressive activity Adult outbred male rats

decreased the number of desquamated endotheliocytes that was the unique morphological criteria for endothelium damage degree

RAF of Abs to eNOS reduced arterial blood pressure (158.515.0 mm Hg vs 160.06.2 mm Hg in control group) and the exhaustion of myocardial fractional flow reserve by 26.9%

RAF of Abs to eNOS increased the number of punished water intakes in Vogel conflict test by

RAF of Abs to eNOS increased the number of entries into open arms of EPM and time spent in open arms up to 1.500.71 and 34.4 8.50 s (vs 00 in control group for both parameters),

RAF of Abs to eNOS reduced arterial blood pressure by 5.7%

RAF of Abs to eNOS did not affect systemic hemodynamics, did not augment nitroglycerine

Divaza decreased the content of diene conjugates in the cerebral hemispheres by 9.7- 27.8% in the heptane fraction and by 7.5-47.4% in isopropanol fraction. The accumulation of 2 thiobarbituric acid-reactive products was reduced by 20.1-

Divaza increased the value of neurite outgrowth by 9.6%

Divaza increased the latency of the entry into the dark compartment of CPAR experimental chamber by 3-

Divaza increased the number of the wheel turns in Nomura

1.6-times

respectively

effects

27.5%

times

Divaza improved acetylcholine-induced relaxation of aorta vascular smooth muscle by 1.4-times [40]

[42]

[42]

[43]

[44]

Unpublished data

[45]

Unpublished data

[46]

[47]


*Association between Peripheral Blood Inflammatory Markers, Endothelial Dysfunction Markers,… DOI: http://dx.doi.org/10.5772/intechopen.88693*

**Appendix**

RAF of Abs to S100

RAF of Abs to eNOS

**114**

Endothelio-protective

activity

Pharmacodynamics

Neuroprotective activity

*Basic and Clinical Understanding of Microcirculation*

**Drug Studied activity Test system Results Ref**

RAF of Abs to S100 added to the incubation medium accurately before or 20 h before the hypoxia induction increased the number of survived cells by 1.8- and 2.1-

RAF of Abs to S100 increased the number of the wheel turns in Nomura forced swimming test by 1.8-2.2-times

RAF of Abs to S100 decreased the duration of immobility in Porsolt forced swimming test

RAF of Abs to S100 increased the number of punished water intakes in Vogel conflict test by

RAF of Abs to S100 increased the number of entries into open arms of EPM, the time spent in open arms and the number of leanings over the edge of the maze by 1.9-, 5.4- and 4.9 times, respectively

RAF of Abs to S100 increased the number of entries into the center of the open field up to 2.40.7 vs 00 in control

RAF of Abs to S100 increased the number of punished water intakes in Vogel conflict test by

RAF of Abs to eNOS reduced arterial blood pressure (184.37.0 mm Hg vs 190.36.7 mm Hg in L-NAMEgroup) and the exhaustion of myocardial fractional flow

RAF of Abs to eNOS improved microcirculation in the ischemic area, stimulated neoangiogenesis and promoted recruitment of additional capillaries into general

RAF of Abs to eNOS improved the metabolism of endothelial capillaries and significantly

[33]

[34, 35, 36]

[34, 36, 37, 38, 39]

[34, 39]

[34, 39]

[38]

[40]

[41]

[35]

times, respectively

by 1.6-times

1.4-3.2-times

group

1.5-times

reserve by 11%

circulation;

Mouse neuroblastoma C-1300 cells deprived of glucose and O2

Antidepressive activity Adult outbred male

Anxiolytic activity Adult outbred male

albino rats

albino rats

Adult Rj:Wistar (Han) male rats

Adult Wistar male rats with NO deficiency, induced by L-NAME

Adult Wistar male rats with NO deficiency, induced by L-NAME


**Drug Studied activity Test system Results Ref** CHO and CHO-K1

*Association between Peripheral Blood Inflammatory Markers, Endothelial Dysfunction Markers,…*

CHO and CHO-K1

Rat brain cortex neuronal cells

Human leukemic Тcell line (Jurkat); human breast cancer cell line (MCF-7)

Cavernous bodies of adult Wistar male rats

Segments of vas deferens of male albino Dunkin-Hartley guinea-pigs

Notes*: \* - adapted from [*73*], CPAR - conditioned passive avoidance reflex, EPM - elevated plus maze, LPT - long-*

*Experimental studies of pharmacological activity and mechanisms of action of RAF of Abs to S100, RAF of Abs*

cells

RAF of Abs to S100 increased specific radioligands binding to 5-HT1F-, 5-HT2B-, 5- HT2Cedied- and 5-HT3 receptors by 142.0%, 131.9%, 149.3% and 120.7%,

[51]

[51]

[52]

[51]

[53]

[54]

respectively; also RAF of Abs to S100 exerted antagonist effect at 5-HT1B-receptors inhibiting their functional activity by 23.2% and agonist effect at 5- HT1A-receptors enhancing their functional activity by

RAF of Abs to S100 increased specific radioligand binding to D3-receptors by 126.3% and exerted antagonism at D3 receptors inhibiting their functional activity by 32.8%

RAF of Abs to S100 decreased specific radioligand binding to NMDA-receptors by 39.1%

RAF of Abs to S100 decreased specific radioligand binding to native and recombinant human σ1-receptors by 75.3% and 40.3%, respectively

RAF of Abs to eNOS increased eNOS activity, the content of NO derivates and the content of cGMP by 2.4-, 1.3- and 4 times, respectively

Divaza increased the amplitude of tissue contraction induced by standard agonist by 2-times

28.0%

cells

*DOI: http://dx.doi.org/10.5772/intechopen.88693*

Involvement of dopaminergic system in the realization of RAF of Abs to S100 effects

Involvement of glutamatergic system in the realization of RAF of Abs to S100 effects

Involvement of σ1 receptor in the realization of RAF of Abs to S100 effects

Effects on vascular endothelial function

Divaza Involvement of σ1 receptor in the realization of Divaza

effects

*to eNOS and combination drug Divaza.*

*term potentiation.*

**Appendix 1.**

**117**

RAF of Abs to eNOS



Notes*: \* - adapted from [*73*], CPAR - conditioned passive avoidance reflex, EPM - elevated plus maze, LPT - longterm potentiation.*

#### **Appendix 1.**

**Drug Studied activity Test system Results Ref**

Hippocampal slices (400 μm) of mature Wistar rats

Isolated neurons of Helix pomatia

Adult outbred male albino rats

Adult outbred male

CHO cells expressing human GABA receptors

Adult outbred male

rats

rats

Anxiolytic activity Adult outbred male rats

*Basic and Clinical Understanding of Microcirculation*

Mechanisms of action

Influence on Abs to S100 activity (ability to

Influence on electrical properties of cell membranes

induce LTP)

Involvement of GABAA-ergic system in the realization of RAF of Abs to S100 effects

Involvement of GABAB-ergic system in the realization of RAF of Abs to S100 effects

Involvement of serotonergic system in the realization of RAF of Abs to S100 effects

**116**

RAF of Abs to S100

forced swimming test by 1.8-

Divaza increased the number of punished water intakes in Vogel conflict test by 2.5-times

Abs to S100 inhibited the induction of LPT, whereas RAF of Abs to S100 offset this inhibiting activity

current channels

Bicuculline and picrotoxin (GABAA-receptors antagonists) decreased the anxiolytic effect of RAF of Abs to S100 in Vogel conflict test by 1.8- and 1.6-times, respectively

Baclofen (GABAB-receptors agonist) decreased the anxiolytic effect of RAF of Abs to S100 in Vogel conflict test by 2.2-times, whereas phaclofen (GABAB-receptors antagonist) increased it by 1.4 times; both baclofen and phaclofen decreased

antidepressive effect of RAF of Abs to S100 in Nomura's forced swimming test by 1.5- and 1.7-

RAF of Abs to S100 exerted antagonism at GABAB1A/B2 receptors inhibiting agonistinduced responses by 30.2% and also inhibited specific binding of ([3,4-3H] cyclohexylmethyl)phosphinic acid ([3H]-CGP54626) to GABAB1A/B2-receptors by

Ketanserin (5-НТ2 receptors antagonist) decreased both the anxiolytic effect of RAF of Abs to S100 in Vogel conflict test and antidepressive effect of RAF of Abs to S100 in Nomura forced swimming test by 1.9 and 2-times, respectively

times, respectively

25.8%

RAF of Abs to S100 suppressed generation of action potential in a dose-dependent manner and increased the maximal speed of its growth via changing the volt-ampere characteristics of the incoming

[47]

[48]

[49]

[37]

[50]

[51]

[36]

times

*Experimental studies of pharmacological activity and mechanisms of action of RAF of Abs to S100, RAF of Abs to eNOS and combination drug Divaza.*

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