Imipramine is the prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group.
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1 moreTitle: Parasympatholytic activity of psychoactive drugs in rat brain mitochondria Nag M, Basu PS, Nandi N Ref: Indian Journal of Experimental Biology, 33:462, 1995 : PubMed
Chlorpromazine, imipramine and amphetamine at a concentration of 0.66, 1.33 and 13.3 x 10(4) M in vitro inhibited acetyl cholinesterase activity by 16, 23 and 31% respectively in rat brain mitochondria. No change in enzyme activity was induced by these drugs in vivo. There is little cholinergic facilitation through acetylcholinesterase inhibition in the presence of psychoactive drugs.
        
Title: Neurochemical and histopathologic alterations characteristic of Pick's disease in a non-demented individual Sparks DL, Danner FW, Davis DG, Hackney C, Landers T, Coyne CM Ref: Journal of Neuropathology & Experimental Neurology, 53:37, 1994 : PubMed
In the course of investigating a large number of non-demented subjects, a 68 year old female dying of coronary artery disease was found to have Pick bodies in her grossly normal brain. Although only mild subcortical gliosis and no neuron loss were observed. Pick bodies were found throughout the brain and occasional balloon cells were noted. Pick bodies and numerous neurons were also ALZ-50 and Tau-1 immunoreactive. Retrospective studies indicated a lack of overt intellectual decline or depression in this individual. Frontal, temporal and occipital poles, amygdala, hypothalamus and nucleus basalis of Meynert (nbM) were analyzed for ChAT, AChE and MAO-A and -B enzymatic activities and for the binding of 5HT and imipramine. Cholinergic decreases were found only in subcortical structures. Serotonin binding decreases were widespread, excluding the nbM. Altered MAO-B activity was regionally variable, and no differences in MAO-A activity or imipramine binding were observed. Few differences in neurochemical alterations were observed in the current non-demented subject with abundant Pick bodies compared to previous studies of demented Pick's patients. This case strongly suggests that chemical dysfunction and neuropathological features of Pick's disease occur in advance of overt clinical manifestations of the disorder.
        
Title: Chemical modification of the bifunctional human serum pseudocholinesterase. Effect on the pseudocholinesterase and aryl acylamidase activities Boopathy R, Balasubramanian AS Ref: European Journal of Biochemistry, 151:351, 1985 : PubMed
The effect of chemical modification on the pseudocholinesterase and aryl acylamidase activities of purified human serum pseudocholinesterase was examined in the absence and presence of butyrylcholine iodide, the substrate of pseudocholinesterase. Modification by 2-hydroxy-5-nitrobenzyl bromide, N-bromosuccinimide, diethylpyrocarbonate and trinitrobenzenesulfonic acid caused a parallel inactivation of both pseudocholinesterase and aryl acylamidase activities that could be prevented by butyrylcholine iodide. With phenylglyoxal and 2,4-pentanedione as modifiers there was a selective activation of pseudocholinesterase alone with no effect on aryl acylamidase. This activation could be prevented by butyrylcholine iodide. N-Ethylmaleimide and p-hydroxy-mercuribenzoate when used for modification did not have any effect on the enzyme activities. The results suggested essential tryptophan, lysine and histidine residues at a common catalytic site for pseudocholinesterase and aryl acylamidase and an arginine residue (or residues) exclusively for pseudocholinesterase. The use of N-acetylimidazole, tetranitromethane and acetic anhydride as modifiers indicated a biphasic change in both pseudocholinesterase and aryl acylamidase activities. At low concentrations of the modifiers a stimulation in activities and at high concentrations an inactivation was observed. Butyrylcholine iodide or propionylcholine chloride selectively protected the inactivation phase without affecting the activation phase. Protection by the substrates at the inactivation phase resulted in not only a reversal of the enzyme inactivation but also an activation. Spectral studies and hydroxylamine treatment showed that tyrosine residues were modified during the activation phase. The results suggested that the modified tyrosine residues responsible for the activation were not involved in the active site of pseudocholinesterase or aryl acylamidase and that they were more amenable for modification in comparison to the residues responsible for inactivation. Two reversible inhibitors of pseudocholinesterase, namely ethopropazine and imipramine, were used as protectors during modification. Unlike the substrate butyrylcholine iodide, these inhibitors could not protect against the inactivation resulting from modification by 2-hydroxy-5-nitrobenzyl bromide, N-bromosuccinimide and trinitrobenzenesulfonic acid. But they could protect against the activation of pseudocholinesterase and aryl acylamidase by low concentrations of N-acetylimidazole and acetic anhydride thereby suggesting that the binding site of these inhibitors involves the non-active-site tyrosine residues.
        
1 lessTitle: Parasympatholytic activity of psychoactive drugs in rat brain mitochondria Nag M, Basu PS, Nandi N Ref: Indian Journal of Experimental Biology, 33:462, 1995 : PubMed
Chlorpromazine, imipramine and amphetamine at a concentration of 0.66, 1.33 and 13.3 x 10(4) M in vitro inhibited acetyl cholinesterase activity by 16, 23 and 31% respectively in rat brain mitochondria. No change in enzyme activity was induced by these drugs in vivo. There is little cholinergic facilitation through acetylcholinesterase inhibition in the presence of psychoactive drugs.
        
Title: Neurochemical and histopathologic alterations characteristic of Pick's disease in a non-demented individual Sparks DL, Danner FW, Davis DG, Hackney C, Landers T, Coyne CM Ref: Journal of Neuropathology & Experimental Neurology, 53:37, 1994 : PubMed
In the course of investigating a large number of non-demented subjects, a 68 year old female dying of coronary artery disease was found to have Pick bodies in her grossly normal brain. Although only mild subcortical gliosis and no neuron loss were observed. Pick bodies were found throughout the brain and occasional balloon cells were noted. Pick bodies and numerous neurons were also ALZ-50 and Tau-1 immunoreactive. Retrospective studies indicated a lack of overt intellectual decline or depression in this individual. Frontal, temporal and occipital poles, amygdala, hypothalamus and nucleus basalis of Meynert (nbM) were analyzed for ChAT, AChE and MAO-A and -B enzymatic activities and for the binding of 5HT and imipramine. Cholinergic decreases were found only in subcortical structures. Serotonin binding decreases were widespread, excluding the nbM. Altered MAO-B activity was regionally variable, and no differences in MAO-A activity or imipramine binding were observed. Few differences in neurochemical alterations were observed in the current non-demented subject with abundant Pick bodies compared to previous studies of demented Pick's patients. This case strongly suggests that chemical dysfunction and neuropathological features of Pick's disease occur in advance of overt clinical manifestations of the disorder.
        
Title: A peptidase activity exhibited by human serum pseudocholinesterase Boopathy R, Balasubramanian AS Ref: European Journal of Biochemistry, 162:191, 1987 : PubMed
The identity of a peptidase activity with human serum pseudocholinesterase (PsChE) purified to apparent homogeneity was demonstrated by co-elution of both peptidase and PsChE activities from procainamide-Sepharose and concanavalin-A--Sepharose affinity chromatographic columns; comigration on polyacrylamide gel electrophoresis; co-elution on Sephadex G-200 gel filtration and coprecipitation at different dilutions of an antibody raised against purified PsChE. The purified enzyme showed a single protein band on gel electrophoresis under non-denaturing conditions. SDS gel electrophoresis under reducing conditions, followed by silver staining, also gave a single protein band (Mr approximately equal to 90,000). Peptidase activity using different peptides showed the release of C-terminal amino acids. Blocking the carboxy terminal by an amide or ester group did not prevent the hydrolysis of peptides. There was no evidence for release of N-terminal amino acids. Potent anionic or esterase site inhibitors of PsChE, such as eserine sulphate, neostigmine, procainamide, ethopropazine, imipramine, diisopropylfluorophosphate, tetra-isopropylpyrophosphoramide and phenyl boronic acid, did not inhibit the peptidase activity. An anionic site inhibitor (neostigmine or eserine) in combination with an esterase site inhibitor (diisopropylfluorophosphate) also did not inhibit the peptidase. However, the choline esters (acetylcholine, butyrylcholine, propionylcholine, benzoylcholine and succinylcholine) markedly inhibited the peptidase activity in parallel to PsChE. Choline alone or in combination with acetate, butyrate, propionate, benzoate or succinate did not significantly inhibit the peptidase activity. It appeared that inhibitor compounds which bind to both the anionic and esteratic sites simultaneously (like the substrate analogues choline esters) could inhibit the peptidase activity possibly through conformational changes affecting a peptidase domain.
        
Title: Chemical modification of the bifunctional human serum pseudocholinesterase. Effect on the pseudocholinesterase and aryl acylamidase activities Boopathy R, Balasubramanian AS Ref: European Journal of Biochemistry, 151:351, 1985 : PubMed
The effect of chemical modification on the pseudocholinesterase and aryl acylamidase activities of purified human serum pseudocholinesterase was examined in the absence and presence of butyrylcholine iodide, the substrate of pseudocholinesterase. Modification by 2-hydroxy-5-nitrobenzyl bromide, N-bromosuccinimide, diethylpyrocarbonate and trinitrobenzenesulfonic acid caused a parallel inactivation of both pseudocholinesterase and aryl acylamidase activities that could be prevented by butyrylcholine iodide. With phenylglyoxal and 2,4-pentanedione as modifiers there was a selective activation of pseudocholinesterase alone with no effect on aryl acylamidase. This activation could be prevented by butyrylcholine iodide. N-Ethylmaleimide and p-hydroxy-mercuribenzoate when used for modification did not have any effect on the enzyme activities. The results suggested essential tryptophan, lysine and histidine residues at a common catalytic site for pseudocholinesterase and aryl acylamidase and an arginine residue (or residues) exclusively for pseudocholinesterase. The use of N-acetylimidazole, tetranitromethane and acetic anhydride as modifiers indicated a biphasic change in both pseudocholinesterase and aryl acylamidase activities. At low concentrations of the modifiers a stimulation in activities and at high concentrations an inactivation was observed. Butyrylcholine iodide or propionylcholine chloride selectively protected the inactivation phase without affecting the activation phase. Protection by the substrates at the inactivation phase resulted in not only a reversal of the enzyme inactivation but also an activation. Spectral studies and hydroxylamine treatment showed that tyrosine residues were modified during the activation phase. The results suggested that the modified tyrosine residues responsible for the activation were not involved in the active site of pseudocholinesterase or aryl acylamidase and that they were more amenable for modification in comparison to the residues responsible for inactivation. Two reversible inhibitors of pseudocholinesterase, namely ethopropazine and imipramine, were used as protectors during modification. Unlike the substrate butyrylcholine iodide, these inhibitors could not protect against the inactivation resulting from modification by 2-hydroxy-5-nitrobenzyl bromide, N-bromosuccinimide and trinitrobenzenesulfonic acid. But they could protect against the activation of pseudocholinesterase and aryl acylamidase by low concentrations of N-acetylimidazole and acetic anhydride thereby suggesting that the binding site of these inhibitors involves the non-active-site tyrosine residues.