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Valproic acid was first synthesized in 1882 by Beverly S. Burton as an analogue of valeric acid , found naturally in valerian .  Valproic acid is a carboxylic acid , a clear liquid at room temperature. For many decades, its only use was in laboratories as a "metabolically inert" solvent for organic compounds. In 1962, the French researcher Pierre Eymard serendipitously discovered the anticonvulsant properties of valproic acid while using it as a vehicle for a number of other compounds that were being screened for antiseizure activity. He found it prevented pentylenetetrazol -induced convulsions in laboratory rats .  It was approved as an antiepileptic drug in 1967 in France and has become the most widely prescribed antiepileptic drug worldwide.  Valproic acid has also been used for migraine prophylaxis and bipolar disorder. 
Mirtazapine is a very strong H 1 receptor inverse agonist and, as a result, it can cause powerful sedative and hypnotic effects.  A single 15 mg dose of mirtazapine to healthy volunteers has been found to result in over 80% occupancy of the H 1 receptor and to induce intense sleepiness.  After a short period of chronic treatment, however, the H 1 receptor tends to desensitize and the antihistamine effects become more tolerable. Many patients may also dose at night to avoid the effects, and this appears to be an effective strategy for combating them. Blockade of the H 1 receptor may improve pre-existing allergies , pruritus , nausea, and insomnia in afflicted individuals. It may also contribute to weight gain, however. In contrast to the H 1 receptor, mirtazapine has only low affinity for the muscarinic acetylcholine receptors , although anticholinergic side effects like dry mouth, constipation, and mydriasis are still sometimes seen in clinical practice.