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Biomedical subjects

S Maayani

Publications and source records attributed to S Maayani.

103 records · Page 6Linked to original sources
PubMed1977

Antimuscarinic properties of antidepressants: dibenzepin (Noveril).

The antimuscarinic potency of dibenzepin (Noveril) was estimated by measuring (a) central in vivo effects in mice (antihypothermia and antitremor, both induced by oxotremorine), (b) peripheral in vivo activity (mydriasis caused by systemic administration of the drug), (c) the effects of dibenzepin on isolated smooth muscle from guinea pig ileum, and (d) in vitro determination of the affinity constant of dibezepine toward the muscarinic binding sites in whole mouse-brain homogenate. The data allowed the construction of a normalized antimuscarinic potency scale for some of the common tricyclic antidepressants. With a value of 1 for scopolamine, the following relative anticholinergic potencies were calculated: dibenzepin--1/600, nortriptylne--1/300, imipramine - 1/200, and amitriptyline - 1/75. These values suggest an explanation for the absence of clinically detectable anticholinergic side effects during treatment of depression with high doses of dibenzepin. Structural and spatial interrelations among various tricyclic antidepressants and scopolamine are discussed.

Animals↗
PubMed1977

Antagonism of histamine-activated adenylate cyclase in brain by D-lysergic acid diethylamide.

D-Lysergic acid diethylamide and D-2-bromolysergic acid diethylamide are competitive antagonists of the histamine activation of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); E.C. 4.6.1.1] in broken cell preparations of the hippocampus and cortex of guinea pig brain. The adenylate cyclase is linked to the histamine H2-receptor. Both D-lysergic acid diethylamide and D-2-bromolysergic acid diethylamide show topological congruency with potent H2-antagonists. D-2-Bromolysergic acid diethylamide is 10 times more potent as an H2-antagonist than cimetidine, which has been the most potent H2-antagonist reported, and D-lysergic acid diethylamide is about equipotent to cimetidine. Blockade of H2-receptors could contribute to the behavioral effects of D-2-bromolysergic acid diethylamide and D-lysergic acid diethylamide.

Adenylyl Cyclases↗
PubMed1975

A rapid method for measuring miotic activity of drugs in the intact mouse eye.

A rapid and precise method for evaluating the miotic activity of cholinergic drugs has been developed based on Long's method for measuring the rate of mydriasis. The rate of reversal of mydriasis developed previously in the intact mouse eye by a mild mydriatic (phenycyclidine) is used to evaluate the miotic activity. The method provides a useful tool for measuring and comparing the miotic activity of acetylcholine agonists and cholinesterase inhibitors.

Amides↗
PubMed1975

Drugs affecting the cholinergic system in the intact mammalian eye. I. Evaluation of the miotic activity of acetylcholine-like drugs in the mouse eye.

The effect of concentration and pH on the miotic activity of five acetylcholine-like drugs were studied in the intact mouse eye. The data suggests that it is mainly the nonionized form of the drug which contributes to its miotic activity. Acetylcholine-like drugs, degradable by cholinesterases, exert their miotic activity at higher concentrations than do those which are resistant to enzymatic hydrolysis. More active acetylcholine-like drugs appear to be less sensitive to concentration changes.

Acetylcholine↗
PubMed1973

Acetylcholine-like molecular arrangement in psychomimetic anticholinergic drugs.

A study of the relation between the psychotropic activity and the antagonism to acetylcholine observed for some heterocyclic amino esters and compounds of the phencyclidine series suggests some common molecular structural requirements for their properties. Criteria obtained from quantum mechanical calculations of acetylcholine-like molecules indicate that their molecular reactivity with the cholinergic receptor site follows a certain dynamic interaction pattern. This pattern suggests a certain molecular arrangement essential for the interaction, which is based on the electronic properties of the molecules and therefore remains valid for the evaluation of compounds which lack any apparent similarity to acetylcholine. This type of molecular arrangement is shown to be shared by both activators and inhibitors of the acetylcholine receptor discussed here, thus supporting the hypothesis of their binding to a common receptor. The differences in biological activity are attributed to the effect of molecular structural factors which are not commonly included in the molecular arrangement based on the active groups of acetylcholine. The role of such factors is revealed by a study of the observed differences in the cholinergic and psychomimetic activities of related pairs of isomers and enantiomers of the molecules investigated. Structural factors which interfere with the conformational changes occurring in the receptor protein induced by an activator are characterized through differences obtained by the comparative investigation of the activities of the agonist acetate and the antagonist benzilate amino esters of quinuclidine, tropine, and pseudotropine. The same factors are shown in studies of the phencyclidine series to contribute to the antagonism to acetylcholine activity that is closely related to the psychomimetic activity of these drugs in the central nervous system. Similarly, phencyclidine derivatives in which the characteristic acetylcholine-like molecular arrangement is modified by various substitutions are shown to loose both anticholinergic and psychotropic behavior. This close correlation is supported by the identification of molecular regions which will generate the proper molecular arrangement in local anesthetics and morphine, compounds which are known to be involved in cholinergic mechanisms.

Acetylcholine↗
PubMedDate not supplied

Kinetics of response and drug action.

Vascular smooth muscle tone is modulated in vivo by the functional interaction of a variety of vasoconstrictor and vasodilator stimuli. Endogenous substances (e.g., epinephrine) acting on smooth muscle, simultaneously activate alpha-adrenergic receptors (alpha-AR) eliciting contraction and beta-adrenergic receptors (beta-AR) which relax the muscle. This study characterizes the beta-adrenergic response in the isolated rabbit aorta precontracted with phenylephrine (PE) or serotonin (5-hydroxytryptamine [5-HT]). The beta-adrenergic agonist isoproterenol (ISO) produces a biphasic response that is composed of a rapid relaxation followed by a slower regaining of tension identified as desensitization. An exploratory kinetic model that describes both relaxation and desensitization as first order processes provides a good description of the experimental data. The five parameters used to describe the ISO response are: the observed rate constants for relaxation and desensitization (krel and kdes), the fractional magnitudes of the changes in tension for the two processes (R/C) and D/R), and the observed delay in the onset of the desensitization response, td. The krel and R/C were dependent on concentration of ISO in a saturable manner in rings precontracted with either 1 mumol/L PE or 1 mumol/L 5-HT and inversely related to the concentration of the contractile agonist. Yet, although the degree of fractional relaxation in the presence of PE covered the full range, that of 5-HT extended over a range of 20%. This behavior leads to the conclusion that the functional interaction between the contractile and relaxing stimuli is non additive. No dependence on the concentration of ISO was observed for D/R, kdes, and td.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗