Effects of different classes of antiepileptic drugs on brain-stem pathways

Antiepileptic drugs probably act by preventing the spread of the abnormal paroxysmal activity from the epileptogenic focus to surrounding normal neurons. An investigation of the mechanism of action of established anticonvulsant drugs on normal neuronal systems may therefore offer useful insights into the pathogenesis of the seizure disorders that these drugs serve to control. Antiabsence drugs (ethosuximide, valproate) depress reticular inhibitory pathways. Drugs effective against generalized tonic-clonic seizures (phenytoin, carbamazepine, valproate) depress reticular excitatory pathways. Drugs that are also effective against trigeminal neuralgia (phenytoin, carbamazepine) also depress afferent excitation and facilitate segmental inhibition in the trigeminal complex. Drugs that depress afferent excitation and facilitate segmental inhibition but do not depress the reticular system (baclofen) are effective against trigeminal neuralgia but do not have clinical antiepileptic properties. These observations indicate that the ability to depress the reticular core is an important characteristic of antiepileptic drugs, and suggest that the reticular core is involved in the spread and generalization of clinical seizures.     

Effects of psychotropic drugs on neurotransmitters in man

Primary biochemical profiles of antidepressants and neuroleptics are summarized in comparison to their actual effects on monoamine neurotransmitters in humans during the time period when clinical response emerges. Even the most biochemically specific of these drugs produces effects on at least two monoamines by three to four weeks. Interestingly, taking into account relative changes in dopamine and serotonin metabolites in cerebrospinal fluid relates better to the primary biochemical action(s) of each drug than do absolute changes. Moreover, monoamine changes after drugs are in the opposite direction to those after ECT, suggesting that balance among rather than shifts in single neurotransmitters is the relevant target of major psychotropic drugs.     

Elimination of F'lac plasmid by different psychotropic drugs and some related compounds.

Desipramine, trimipramine, protriptyline, noxiptyline, promazine, trimeprazine, triflupromazine and chlorprothixene methoiodide eliminated the F'lac plasmid of Escherichia coli, while thiazinanum, toluidine blue, lidocaine and procaine were ineffective in this respect. The plasmid eliminating action of the drug ceased in the presence of 0.05 M magnesium sulphate. Methylene blue did not inhibit plasmid elimination by the psychotropic drugs, and in presence of the dye even lidocaine and procaine became effective. Based on plasmid elimination in the presence of methylene blue and on the selective effects of the lon- mutant, the plasmid eliminating mechanism of psychotropic drugs seems to differ from that of acridine orange.     

Mutagenic activity of psychotropic drugs]

Mutagenic activity of 33 psychotropic drugs was studied in Drosophila metanogaster according to the CLB method. The drugs are the following: leponex, neuleptil, randolectil, teralen, chlorprotixen, TPS-23, navane, pimosid, difenisid, rudotel, eunoktin, radedorm, meprobamat, trioxasin, elenium, napoton, aponal, lorasepam, nuredal, oxyphenonat, safrasin, surmantil, amitriptilin, prothioden, melipramin, saroten, tegretol, phenobarbital, diakarb, benzonal, suksilep, morpholep, sydnocarb. The increase in the mutation rate was induced by leponex (1.37% in adults and 1.21% in larvae), difenisid (1.18% in adults), two forms of the same drug eunoktin and radedorm (about 1.6% in adults), safrasin (1.06% in imago), saroten (1,36% in imago), phenobarbital (2.02% in imago). Even a slight increase of mutagenicity of widely spread psychotropic drugs is a very serious factor which needs further investigation and specification in other models and organisms.