Surendra S. Parmar

Biochemical study of anti-inflammatory and anti-arthritic properties of glycyrrhetic acid☆

Abstract The anti-inflammatory activity of glycyrrhetic acid, methyl glycyrrhetic acid and glycyrrhetic acid diacetate was found to be similar to hydrocortisone on the formalininduced arthritis in albino rats. Methyl glycyrrhetic acid and glycyrrhetic acid diacetete were more potent anti-inflammatory agents when compared with glycyrrhetic acid. Glycyrrhetic acid, methyl glycyrrhetic acid and hydrocortisone prevented the elevation of S-GOT and S-GPT during inflammation. These agents reduced the S-GPT level and not the S-GOT level in normal rats. ATPase activity in brain and liver homogenates remained unaltered during inflammation but was significantly elevated by these agents. The significance of these biochemical changes is discussed.

Antagonism between stereoisomeric amphetamines, amphetamine derivatives and other monoamine oxidase inhibitors

Abstract An antagonism between stereoisomeric amphetamines, amphetamine derivatives and other monoamine oxidase inhibitors has been investigated. The monoamine oxidase activity of isolated rat liver mitochondria was measured manometrically and the values checked by spectrophotofluorometric estimation of tyramine substrate to show that the oxygen uptake reflects the true enzyme activity under present experimental conditions. It was also found that concentrations of amphetamine and an amphetamine derivative P-1882 ( p -S-methylamphetamine), without effecting the enzyme activity, protected monoamine oxidase against inhibition by iproniazid, pheniprazine tranylcypromine, nialamide and P-1726 ( p -trifluoromethylamphetamine). Another amphetamine derivative P-1726 was found to be a more potent and more persistent inhibitor of monoamine oxidase than either amphetamine or P-1882. On the other hand such low concentrations of P-1726 had no protective effect on the inactivation caused by other inhibitors. Further, with respect to both direct inhibition and protection against other inhibitors, d -amphetamine was more active than the corresponding l -isomer.

Interrelationship of chemical structure and antiacetylcholinesterase activity of disubstituted quinazolones

Abstract Antiacetylcholinesterase activity of quaternary ammonium compounds of 2-methyl-3(2′-)pyridyl-4-quinazolone [QZ-2′] and 2-methyl-3(4′-)pyridyl-4-quinazolone [QZ-4′] has been investigated. Acetylcholinesterase activity of rat brain homogenates was determined colorimetrically, with acetylthiocholine as substrate. Both series of these quaternary compounds inhibited acetylcholinesterase competitively. With QZ-4′ derivatives, it was found that an increased inhibition was dependent upon the number of carbon atoms of the alkyl chain at the pyridinium nitrogen, whereas no such effect was observed with QZ-2′ compounds. The possible mechanism of action for such dissimilarity in enzyme inhibition has been discussed.

Effects of enzyme inhibitors on the adrenergic mechanisms in isolated vas deferens preparation

Abstract THE presence of adrenaline in the adrenergic axon innervating the smooth muscle layer of the vas deferens of guinea pig was demonstrated by fluorescence method. 1 The vas deferens contain both adrenaline and nor-adrenaline. 2 The enzymes responsible for their inactivation are monoamine oxidase (MAO) and catechol methyl transferase (CMT). 3 The present investigation was undertaken to gain further information on the role of the inhibitors sof MAO and CMT on the adrenergic transmission in the isolated vas deferens preparation.

Styrylquinazolones as monoamine oxidase inhibitors

Abstract Several substituted styrylquinazolones were synthesized and tested for their ability to inhibit the oxidative deamination of kynuramine by monoamine oxidase (MAO) from the rat brain. Quinazolones having hydrazide group were found to be better inhibitors than their corresponding precursor esters. 2-(3-Methoxy-4-hydroxy) styryl-3-(4-benzhydrazide)-4-quinazolone (compound 18) was found to show maximum inhibition of 76% in the series.

Selective stimulation of carboxylesterases metabolizing charged steroid esters by hydrocortisone

We observed a remarkable augmentation in the rate of hydrolytic breakdown of HCHS following exposure to corticosteroid therapy. This underscores the need for a careful reappraisal of its dosage in long term therapy. In such an event the uncharged ester may be the preferred drug of choice.

Selective inhibition of β2-adrenergic receptors by 1-(2,4-dimethylanilino)-3-isopropylamino-2-propanol

1-(2,4-Dimethylanilino)-3-isopropylamino-2-propanol (RB2) was synthesized and evaluated for its selective β2-receptor blocking property. RB2 was found to antagonize selectively vasodepressor β2-response.of isoprenaline without affecting the cardio accelerator β2-response. As an antagonist of β2-receptor, RB2 was found to be equipotent to 1-(4′-nitrophenyl)-2-isopropylaminoethanol (INPEA), used as a standard β-receptor antagonist for comparison.

Mechanism of action of dopamine and other precursors of noradrenaline on the guinea-pig isolated hypogastric nerve vas deferens preparation

Abstract The effect of 3, 4-dihydroxyphenylethylamine (dopamine) and other precursors of noradrenaline was investigated on the responses of guinea-pig isolated vas deferens to nerve stimulation. Amongst these precursors tyrosine and 3, 4-dihydroxyphenylalanine (DOPA) were found to be inactive whereas dopamine potentiated these responses. The potentiating effect of dopamine was studied in preparations obtained from normal, reserpinized, α-methyl-DOPA, and disulfiram treated guinea-pigs. Evidence is presented in support of a direct action of dopamine on the α-adrenergic receptors although its action by the release of catecholamines from storage site(s) or by the enzymatic conversion of dopamine into noradrenaline cannot be completely ruled out.

SYNTHESIS OF SOME SUBSTITUTED BENZODIAZEPINES AS POSSIBLE CNS DEPRESSANT DRUGS

A new series of 2,3-cyclopentano-3,4-dihydro-4-spirocyclopentano-1,5-benzodi azepine which are substituted in 5-position with beta-N-heterocycloethyl or gamma-N-heterocyclo-n-propyl groups have been synthesized and evaluated for their CNS depressant activity including anticonvulsant, analgesic and pentobarbital induced hypnosis. These compounds were also investigated for their ability to inhibit in vitro succinate dehydrogenase (SDH). In most of the compounds an appreciable CNS depressant activity has been found to be associated with the compounds possessing good SDH inhibitory activity. Low toxicity of these compounds was reflected by their high approximate LD50 values.

Structural consideration in the inhibition of rat brain acetylcholinesterase

from that released by dimethylphenylpiperazinium. In addition, the different time course of inhibition implied that the acetylcholine was liberated under different circumstances by the two drugs. The known property of mipafox to discriminate between the two types of cholinesterase (Fig. 1. ; Holmstedt, 1957) would favour the explanation that the acetylcholine released by 5-hydroxytryptamine is hydrolysed by a cholinesterase with different properties from that which hydrolyses the acetylcholine released by dimethylphenylpiperazinium or acetylcholine added exogenously, and it is difficult to imagine how this could arise unless 5-hydroxytryptamine is acting on a nerve-pathway independent from that activated by dimethylphenylpiperazinium. The greater potentiation of 5-hydroxytryptamine than dimethylpiperazinium by mipafox can be explained only by a difference in the amount of or nature of the cholinesterase at a separate nerve-ending. The simplest explanation suggested by these experiments is that 5-hydroxytryptamine and dimethylphenylpiperazinium activate different nerve-pathways ; the acetylcholine released by 5-hydroxytryptamine being hydrolysed mostly by acetylcholinesterase whereas that released by dimethylphenylpiperazinium, and also exogenous acetylcholine, being hydrolysed by a mixture of both butyryl and acetylcholinesterase.