**5. References**

532 Pharmacology

exploratory activity, typical for sedative pharmaceutical compositions. It coadministration (50 mg/Kg) with thiopental, at experimental dosis, increase the number of sleeping animals (65%), a typical depressing action on CNS. The administration of DHAA, at all dosis evaluated, didn't protect animals for PTZ induced convulsions. The experimental data obtained in the Labyrinth in cross model didn't show any relevant results. In the Amphetamine-induced stereotipia model DHAA decreases the stimulant action produced by the subcutaneously administration of 1,5 mg / Kg of amphetamine, in the hypothetically pathways described above. The acute toxicity (DL50 > 5000 mg/Kg) study showed that DHAA had not any toxic effects at dosis concentrations used and

It is noteworthy that synthetic DHAA has a sedative action on CNS and could be employed as starting raw material for designing of new molecular and pharmacological entities potentially useful in the development of formulation for therapy of CNS pathologies where

Topological studies for determining any QSAR correlation between colophony and

The oleoresin, a raw material isolated from Cuban Pinacea (gen. *Pinus, Pinus caribbaea*), constitutes a sustainable resource for developing potentially useful pro-drugs and pharmacologically active substances as resínic acids, sodium resinate (SR) and dehydroabietic acid. The analytical protocol developed (*all in one* wavelengths-retention time) for common abietanes present in Cuban colophony is simple, time-saving, ecofriendly, employing robust reversed-phase HPLC and offer the possibility to determine and quantify the main diterpenic acids (resínico acids) in the natural and modified mixture. The catalytic synthesis of dehydroabietic acid (DHAA) as a principal active pharmaceutical component from colophony for the potential treatment of neuropsiquiatric dysfunctions and generation of exogenic cannabinoid analogues has been developed under ecological conditions using piritic ash as re-usable catalyst (disproportionation-aromatization) at meso-scale with minimal environmental impact. The neuropharmacological profile (including acute oral toxicity) of SR in rodent behavioural tests was determined; SR reduced spontaneous locomotor activity and aggressive behaviour, increased the number of sleeping animals and prolonged the thiopental-induced sleeping time indicating a the sedative effect of test compound and it might not be related via the GABA or glycine systems. The SR is unable to protect animals against convulsion and death induced by pentylenetetrazole and picrotoxin. The SR (2000 mg/Kg p.o) didn't cause significant toxic symptoms in rats. This finding indicates that the SR can constitute a non conventional source of pharmacological molecular entities with central nervous system depressant activity. The synthetic DHAA has a sedative action on CNS and its acute toxicity (DL50 > 5000 mg/Kg) reveals that DHAA had not any toxic effects at dosis concentrations used and could be employed as starting design structural point for developing molecular entities and series leads with potentially remarkable

could be classified in the GSH in the 5 category.

derivatives and cannabinoids are underway.

de sedative effect is needed.

pharmacological properties.

**4. Conclusion** 


**24** 

James R. Reed

*USA* 

*Department of Pharmacology,* 

**Elucidating the Role of** 

**Biliverdin Reductase in the** 

**Expression of Heme Oxygenase-1** 

**as a Cytoprotective Response to Stress** 

*Louisiana State University Health Sciences Center, New Orleans, LA,* 

Hemin is a cofactor in which an atom of iron is coordinated to the nitrogens of four pyrrole

N N

<sup>N</sup> <sup>N</sup>

Hemin

Many types of enzymes in living systems use hemin as a prosthetic group to catalyze oxidation/reduction reactions or for the binding/transport of reactive molecules (e.g. oxygen). For instance, several cytochromes of the mitochondrial electron transport chain are "heme" enzymes as are the major drug/xenobiotic-metabolizing enzymes of the endoplasmic reticulum, the cytochromes P450 (CYP or P450). The heme group of the P450s allows these enzymes to use redox chemistry to bind molecular oxygen and cleave the O-O bond, thus forming a reactive, high-valent oxygen species that can insert oxygen into otherwise stable carbon-hydrogen bonds of drugs/xenobiotics (White and Coon, 1980). The unfavorable thermodynamics of this type of reaction has caused the P450s to be likened to "catalytic blowtorches" (Schlichting et al., 2000), and the process is essential for the elimination and clearance of many lipophilic compounds ingested from the environment. Catalase is an important protective heme enzyme that is responsible for degrading

HO O

groups that make up the protoporphyrin IX ring (see figure below).

HO

O

**1. Introduction** 

Tyler, C. B.; K. A. (1982) Miczed: effects of phencyclidine on aggressive behavior in mice. *Pharmacol Biochem Behav* 17: 503-10.

Valzelli, L. (1973) The isolation syndrome in mice. *Psychopharmacology 31:305-20.* 
