Evaluation of isonicotinoyl-.GAMMA.-aminobutyric acid (GABA) and nicotinoyl-GABA as pro-drugs of GABA.

Matsuyama, Kenji; Yamashita, Chikamasa; Noda, Atsuko; Goto, Shigeru; Noda, Hiroshi; Ichimaru, Yasuyuki; Gomita, Yutaka

doi:10.1248/cpb.32.4089

Cited by 28 publications

(16 citation statements)

References 1 publication

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“…85,86 Unlike for 11, earlier studies indicated that hydrolysis to the neurotransmitter was unnecessary for GABAergic activity. 87 CNSdelivery by 19,22, and 23 is shown schematically in Fig. 7.…”

Section: A Neurochemicalsmentioning

confidence: 99%

Targeting drugs to the brain by redox chemical delivery systems

2000

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Section: A Neurochemicalsmentioning

confidence: 99%

Targeting drugs to the brain by redox chemical delivery systems

2000

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“…Picamilon has been synthesized using several methods, often beginning with either nicotinic acid hydrazide or nicotinic acid. The acid group in nicotinic acid is converted to an active ester and condensed with GABA or 2‐pyrrolidinone to yield nicotinoyl‐GABA (picamilon) …”

Section: Introductionmentioning

confidence: 99%

Identification and quantification of vinpocetine and picamilon in dietary supplements sold in the United States

Avula

Chittiboyina

Sagi

et al. 2015

Drug Testing and Analysis

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Vinpocetine and picamilon are drugs prescribed in many countries to treat a variety of cerebrovascular disorders. In the United States, vinpocetine and picamilon have never been approved by the US Food and Drug Administration, but they are both available for sale directly to consumers as dietary supplements. We designed our study to determine the accuracy of supplement labels with regard to the presence and quantity of vinpocetine and picamilon. A validated ultra-high performance liquid chromatography-photodiode-array method was developed for the quantification of vinpocetine and picamilon. The separation was achieved using a reversed phase (C-18) column, photodiode array detection, and water/acetonitrile as the mobile phase. Vinpocetine and picamilon were detected at concentrations as low as 10 and 50 ng/mL, respectively. The presence of vinpocetine and picamilon was confirmed using reference standards. Twenty-three supplements labelled as containing vinpocetine were available for sale at two large supplement retail chains; 17 contained vinpocetine with quantities ranging from 0.3 to 32 mg per recommended daily serving. No vinpocetine was detected in six of the sampled supplements. The supplement label implied that vinpocetine was a constituent of lesser periwinkle in three of the supplements. Of the 31 picamilon supplements available for sale from a variety of retailers: 30 contained picamilon in quantities ranging from 2.7 to 721.5 mg per recommended daily serving. We found that consumers cannot obtain accurate information from supplement labels regarding the presence or quantity of vinpocetine and picamilon.

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“…Received 27 January 2000; Accepted 16 June 2000 [Matsuyama et al, 1984], Schiff bases of GABA (e.g., progabide [Krogsgaard-Larsen et al, 1998]) and the ester of GABA with cholesterol [Shashoua et al, 1984].…”

Section: Introductionmentioning

confidence: 99%

Research on the pharmacochemistry of some GABA and valproic acid derivatives

et al. 2000

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The role of GABA in epilepsy and especially in the action of various antiepileptics has been well established. We have reported the synthesis and pharmacochemical evaluation of a number of GABA and valproic acid derivatives and also the synthesis of two N‐acyl‐2‐pyrrolidinone derivatives. We now report the pharmacochemical evaluation—anticonvulsant and antioxidant activity, and also study of lipophilicity—of the latter two in combination with the synthesis and evaluation of two novel ester derivatives (2‐propylpentyl‐3‐pyridine carboxylate and 3‐pyridinylmethyl 2‐propylpentanoate), which contain the moieties of valproic acid and of 2‐propyl‐1‐pentanol. Anticonvulsant activity was evaluated using the picrotoxin model and the antioxidant potential using the lipid peroxidation method. The study of lipophilicity was performed both by experimental (by reversed phase thin layer chromatography) and calculating (Rekker’s and Hansch/Leo’s fragmental and Suzuki/Kudo’s atom‐based) methods; lipophilicity was also studied in combination with other physicochemical parameters of the above‐mentioned compounds (van der Waals volume, van der Waals area, dipole moment, energy of formation, energy of hydration). In this study, we also include six other derivatives which we synthesized and tested in an earlier study. Only the two ester derivatives exhibited potent anticonvulsant and also antioxidant activity; the 2‐pyrrolidinones did not exhibit significant activity in these experiments. In accordance with our earlier findings, the nicotinoyl and the nicotinyl moieties, in combination with considerable lipophilicity, seem to be suitable groups to confer activity in this type of compound. Good multiple correlation was derived between lipophilicity and energy of hydration and van der Waals volume of the compounds. Drug Dev. Res. 51:143–148, 2000. © 2001 Wiley‐Liss, Inc.

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Evaluation of isonicotinoyl-.GAMMA.-aminobutyric acid (GABA) and nicotinoyl-GABA as pro-drugs of GABA.

Cited by 28 publications

References 1 publication

Targeting drugs to the brain by redox chemical delivery systems

Targeting drugs to the brain by redox chemical delivery systems

Identification and quantification of vinpocetine and picamilon in dietary supplements sold in the United States

Research on the pharmacochemistry of some GABA and valproic acid derivatives

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