ABSTRACT
Medicinal drugs are predominantly, whereas narcotic and psychotropic drugs are exclusively exogenous compounds. Three further fundamental properties of the narcotic/psychotropic compounds of significant abuse potential is that they all are of natural (plant or microbial) origin, they contain a large number of chiral atoms, and they influence the neurotransmission processes in the central nervous system. For some of them, the existence of corresponding endogenous ligands have recently been reported. Since exogenous compounds and their endogenous ligands are assumed to bind the same target moiety of the receptor, several fundamental questions arise: To what extent can stereochemical relationships be established between the exogenous compound and its endogenous counterpart? Do they have superimposable moieties? Are the corresponding chiral atoms of the same configuration? Is there a chiral-genetic relationship between the exogenous and endogenous compound? Theoretical aspects and answers to all these questions are sought for morphine, cocaine, LSD, tetrahydrocannabinol, amphetamine and related molecules.
Subject(s)
Analgesics, Opioid/chemistry , Antipsychotic Agents/chemistry , Narcotics/chemistry , Dopamine/chemistry , Molecular Conformation , Molecular Structure , Serotonin/chemistry , Structure-Activity RelationshipABSTRACT
The percentage of chiral entities among drug, narcotic drug and psychotropic compounds is steadily increasing. Receptors of the human body recognize the enantiomeric forms of constitutionally identical compounds as entirely different chemical agents. Based upon these facts, this paper reports the percentage of chiral compounds in the various pharmacological classes, and related data. Pertinent terms, such as eutomer, distomer, eudismic index, eudismic affinity quotient are defined. Differences in biological activity between eutomers and distomers are exemplified. The pharmacological classes and subclasses of highest chirality, and the "most chiral" active principles are shown. Some puzzling observations on pharmacological behaviour of stereoisomers are highlighted. The necessity of "racemate switch" in the pharmaceutical industry, and the significance of stereo-specific interactions between the drug, narcotic drug and psychotropic ligands, and complementary, "pocket" moieties of the human body are emphasized. Some features of enantiopharmacology, a fledgling science in the interface of stereochemistry and traditional pharmacology are introduced. The statistical treatment of asymmetric compounds in pharmacological classes and subclasses shows that presently, the percentage of chirality in drug categories is more characteristic of the origin of the compound than its target molecule.
Subject(s)
Narcotics/chemistry , Pharmaceutical Preparations/chemistry , Psychotropic Drugs/chemistry , Stereoisomerism , Humans , Molecular Structure , Receptors, Drug/metabolism , Receptors, Opioid/metabolism , Structure-Activity RelationshipABSTRACT
Servoplethysmomanometry (Penáz method) is based on the principle of "vascular unloading" or "arterial volume clamp". It permits continuous recording of the arterial pressure pulse in a finger. We evaluated such a device (Finapres) intraoperatively in cardiac surgical patients and compared the results with those obtained using simultaneous intra-arterial pressure recording. METHODS. Intravenous anesthesia was employed in a total of 31 patients. Invasive pressure monitoring was carried out in the radial artery. The cuff of the Finapres was wrapped around the 3rd finger, either on the same side as the radial cannula (group I, n = 15) or on the contralateral side (group II, n = 16). Quantitative comparison was accomplished for the paired values obtained by the two methods by calculating linear regression equations and correlation coefficients (r), as well as for the differences between the paired values (means, SD, frequency distributions). RESULTS. In group I (ipsilateral recording), r was 0.74 for systolic (SAP), 0.52 for diastolic (DAP), and 0.77 for mean (MAP) pressure. The means +/- SD of the differences (mm Hg) were -1.6 +/- 16.6 (SAP), 4.6 +/- 11.5 (DAP), and 0.2 +/- 11.3 (MAP). In group II (contralateral recording), r was found to be 0.86 (SAP), 0.72 (DAP), and 0.82 (MAP). The mean differences were -2.7 +/- 13.1 (SAP), 4.7 +/- 9.8 (DAP), and -2.6 +/- 10.9 mm Hg (MAP). Prior to cardiopulmonary bypass (CPB) the results of the two methods corresponded to a higher degree than after CPB; during CPB the MAP values correlated poorly in the two groups (r = 0.62). DISCUSSION. The results obtained may be interpreted to mean that the Finapres will enable us to monitor arterial blood pressure continuously with satisfactory reliability when the cuff design has been improved.
