By Manji Husseini K., Robert H. Belmaker

Lithium, the therapy of selection for mania because its usefulness was once first said, has been proven to have diversified results on a number of organic structures, together with electrolyte flux and neurochemistry. fresh advances in mobile and molecular biology promise to supply clinicians with a greater figuring out of the etiology of bipolar illness and new techniques for remedy. Bipolar drugs: Mechanisms of motion offers the therapy and prophylaxis of bipolar illness. greater than forty investigators percentage examine and perception into the neurobiological mechanisms that support to provide an explanation for the strong results of recent antibipolar medications. This entire textual content -Examines valproic acid, lamotrigine, inositol monophosphatase inhibitors, and protein kinase C inhibitors that experience the capability to revolutionize medical perform and supply new hypotheses at the etiology of bipolar affliction -Presents the present figuring out of the mobile mechanisms of motion of mood-stabilizing brokers -Discusses the emergence of valproate as a strong lithium replacement and examines the initial symptoms that lamotrigine should be an efficient choice -Examines the difficulty of withdrawal rebound, which may make lithium useless or maybe counterproductive, and experiences inositol monophosphatase inhibitors that mimic lithium motion in sufferers -Compares lithium, carbamazepine, and valproate and their differential mechanisms, that may shape the root of a "rational polypharmacy" of manic depressive disease -Examines behavioral versions vital within the screening of recent antibipolar compounds and the consequences of antibipolar compounds on fast early genes entire with wide references, tables, and figures, this article is vital studying for any clinician who treats sufferers with bipolar ailment. It completely records the most recent in psychopharmacology, in addition to projecting destiny advances within the therapy of bipolar illness.

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Levine et al. (1993a) gave inositol to 11 unipolar, medication-resistant depressed patients with dramatic results in 7 of the 11. Levine et al. (1995) then performed a controlled double-blind study of 28 depressed patients with 12 g of inositol or placebo for 4 weeks. Inositol treatment reduced Hamilton Rating Scale for Depression scores significantly more than placebo. Kofman and Belmaker (1990) reported behavioral effects of inositol in rats. Levine et al. (1993b) reported that 12 g daily of inositol orally in humans increased CSF inositol by 70%.

Lithium, Phosphatidylinositol Signaling, and Bipolar Disorder 1 20 BIPOLAR MEDICATIONS: MECHANISMS OF ACTION Figure 1–9. Ribbon diagram showing the dimeric structure of human inositol monophosphatase (IMPase); two-metal ions and substrate are also shown in each subunit. α-Helices are shown as thick ribbons, β-sheets as thin ribbons with arrows, and the remainder as a tube. Source. Courtesy of Dr. Howard Broughton, Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, England.

It also seemed important to ask, if lithium inhibits IMPase, whether the enzyme is present in excessive activity in patients with bipolar disorder who were not treated with lithium. After demonstrating that human erythrocytes possess IMPase with properties (Km for inositol 1-phosphate (Ins(1)P) and Ki for lithium) similar to those of other tissues in various species (Agam and Livne 1989), we studied the activity of human red blood cell IMPase in bipolar patients untreated with lithium, in psychiatrically healthy control subjects, and in lithium-treated patients with bipolar disorder (Moscovich et al.

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