J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.49.8.979 on 1 August 1986. Downloaded from

Book reviews 979 In reaching his conclusions nearly every gabide or of fengabine, agents thought to act bamazepine given acutely to rats reduce author who has graced the field of neu- directly or indirectly as GABAmimetics. GABA turnover, but the exact relationship robiology is quoted, and a dazzling array of Evidence from preliminary trials indicating of changes in GABAergic function to ther- ideas are presented. that these compounds are effective anti- apeutic effect in mania is unknown. I would agree with the comments on the depressants is presented in the second half of This volume is beautifully produced. It back cover by Albert Galaburda of the book. Interestingly the subacute admin- has been edited to provide a highly coherent Harvard, "This is a marvellous book,..." istration of progabide to rats lead to similar and readable text. Indeed the contributions M TRIMBLE changes in 5HT2 receptors as does repeated tell a rather too consistent story. Contrary electroshock. Fengabine does not produce opinions are suprisingly absent. The this effect. The proconvulsant action of anti- repeated claims that fengabine is a GABA- depressant drugs is a well known clinical mimetic are taken on trust, but no evidence GABA and Mood Disorders: Experimental problem (both in patients receiving ther- for an agonist action of GABAA or GABAB and Clinical Research (LERS Monograph apeutic doses, and in those taking over- receptors is presented. Series Vol 4). Edited by G Bartholini, KG doses). One contribution in this volume Synthelabo has rendered a valuable ser- Lloyd, PL Morselli. (Pp 240; $32.50.) New attempts to relate this phenomenon to an vice by organising the meeting reported in York: Raven Press, 1985. impairment of GABAergic inhibition. This this the 4th volume in their special mono- remains to be established. However, the use graph series with Raven Press. Scientists and For 25 years manipulation of mono- of GABAmimetics, such as progabide, as clinicians are thus enabled to gain a rapid aminergic synaptic function has provided antidepressants should offer a very real appreciation of current GABA-related the dominant pharmacological approach to advantage in terms of producing an anti- approaches to understanding and treating the treatment of affective disorders. convulsant "side effect". depressive disorders. Their experience with Inhibition of the uptake and further metab- The remarkable studies of Fred Petty on monoamine theories will have taught them olism of noradrenaline or serotonin initially "learned helplessness" in rats provide evi- to temper their enthusiasm with appropriate seemed to be important mechanisms of dence for a GABAergic mechanism (in the scepticism. action of antidepressant drugs. However the hippocampus and perhaps also the neo- BS MELDRUM time-course of these effects clearly does not cortex and lateral geniculate) in the ini- correspond to the time course of therapeutic tiation and prevention of this model of action of the drugs. More recent discoveries depression. They indicate that desipramine Protected by copyright. concerning receptor changes in rat brain fol- acts through a GABAergic mechanism when lowing subacute administration of anti- preventing learned helplessness. Upper Motor Neuron Functions and depressants have appeared likely to resolve The GABA related approach to the Dysfunctions. Recent Achievements in this problem. Thus after 6-12 days "treat- aetiology and therapy of depression can Restorative Neurology Series Volume 1. ment" there is down-regulation of probably be integrated with the existing Edited by Sir John Eccles and Milan R f,-adrenoceptors, with desensitisation of the knowledge of (and lack of comprehension Dimitrijevic. (Pp 346; £87 20.) Basel: fl-adrenoceptor-coupled adenylate cyclase, of) monoaminergic mechanisms. GABA- S Karger AG, 1985. down-regulation of 5HT2 receptors and mimetics accelerate the turnover of nor- biphasic changes in oc2-adrenoceptors. How- adrenaline, and enhance the firing of nor- This book is based on the proceedings of a ever, many anomalous or contradictory adrenergic neurons (probably by specific workshop held in Houston, Texas in Octo- findings have emerged making a comprehen- circuitry acting on the locus coeruleus). ber 1982, "to review achievements in restor- sive explanation of the mechanism of action GABA agonists and GABA-transaminase ative procedures that could modify the of antidepressant drugs in terms of long- inhibitors depress cerebral serotoninergic impaired functions in chronic neurological term changes in monoaminergic receptors transmission (apparently by a direct action diseases". It contains an uneven mixture of untenable (for example, maprotiline does in the nuclei of the dorsal raphe). GABAB basic science and clinical topics that is not not down-regulate fl-adrenoceptors and receptors modulate synaptic release of restricted to upper motor neuron functions. ECT produces an up-regulation in 5HT2 monoamines. Some authors present the results of their receptors and function). The clinical results reported for progabide own work in detail while others have offered http://jnnp.bmj.com/ These considerations and some novel and fengabine are somewhat preliminary. reviews, some brief and others wide-ranging basic findings have lead to a renewed inter- Three double blind studies of progabide in and authoritative. Many of the clinical est in the possible involvement of GABA in comparison with imipramine (n = 11 + 1 1), papers are disappointingly superficial, and the aetiology and pharmacological manage- imipramine (n = 38 + 37) or nortryptiline the early part of the book records a number ment of affective disorders. Perhaps the (n = 9 + 9) show indistinguishable ther- of procedures used for physiological testing most intriguing novel observation reported apeutic outcomes. The true clinical and improving function in various brain and in this volume is the up-regulation of effectiveness of fengabine can only be spinal cord disorders, in which claims of GABAB (baclofen-sensitive) receptors in guessed at from the seven open studies (total clinical usefulness are made but minimal evi- on September 25, 2021 by guest. hippocampus and cortex following subacute n = 76) utilising 3 or 4 weeks of treatment dence presented. This gives the reader a use- administration of electroshock, or of anti- and a variety of dosage schedules. Effects ful review of the range of techniques that depressant drugs of all major pharma- of progabide or fengabine in manic disor- have been tried but little feeling for their cological types (for example desipramine, ders are not reported. The well known clinical value. amitryptiline, viloxazine, nomifensine and studies of Emrich and of Post and colleagues Some chapters stand out as particularly citalopram). This effect is not seen after on the antimanic effects of valproate, good, such as Jacquelin Perry's on the anal- other psychotropic agents, but it is observed oxcarbazepine and carbamazepine are sum- ysis that should be undertaken by ortho- following subacute administration of pro- marised. High doses of valproate or car- paedic surgeons before operating on spastic