Abstract
A series novel of N-palmitoylethanolamide derivatives was synthesized and screened for their anticonvulsant and antidepressant activities. Anticonvulsant activities and neurotoxicities of compounds when injected intraperitoneally (i.p.) were determined by maximal electroshock seizure (MES) test and a rotarod test, respectively, in mice. Only four of the synthesized compounds (3a, 3b, 3c, and 3d) showed anticonvulsant activity at a dose of 100 mg/kg. Six compounds showed reduced immobility durations during the forced swimming test at a dose of 10 mg/kg, indicative of antidepressant activity. Among the compounds, N-(3-hydroxypropyl)cinnamamide (3a) was the most promising compound and significantly reduced the duration of immobility duration by 23.36% at a dose of 10 mg/kg compared with the control (P < 0.01).
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bachur NR, Masek KL, Melmon KL, Udenfriend S (1965) Fatty acid amides of ethanolamine in mammalian tissues. J Biol Chem 240:1019–1024
Balsamo AP, Barili PLL, Crotti P, Macchia D, Macchia F, Pecchia A, Cuttica A, Passerini N (1975) Structure–activity relations in cinnamamides. 1. Synthesis and pharmacological evaluation of some (E)-and(Z)-N-alkyl-, alpha, beta, -dimethylcinnamamides. J Med Chem 18:842–846
Guan LP, Zhao DH, Xiu JH, Sui X, Piao HR, Quan ZS (2009a) Synthesis and anticonvulsant activity of N-(2-hydroxyethyl)amide derivatives. Arch Pharm Chem Life Sci 342:34–40
Guan LP, Wei CX, Deng XQ, Sui X, Piao HR, Quan ZS (2009b) Synthesis and anticonvulsant activity of N-(2-hydroxyethyl)cinnamamide derivatives. Eur J Med Chem 44:3654–3657
Krall RL, Penry JK, White BG, Kupferberg HJ, Swinyard EA (1978) Antiepileptic drug development: II, anticonvulsant drug screening. Epilepsia 19:409–428
Lambert DM, Vandevoorde S, Diependaele G, Govaerts SJ, Robert AR (2001) Anticonvulsant activity of N-palmitoylethanolamide, a putative endocannabinoid, in mice. Epilepsia 42:321–327
Moffet RB (1964) Central nervous system depressants. VI. Polymethoxyphenyl esters and amides. J Med Chem 7:319–325
Porsolt RD (1981) Behavioral despair. In: Enna SJ, Malick JB, Richelson E (eds) Antidepressants: neurochemical, behavioral and clinical perspectives. Raven, New York, pp 121–139
Porsolt RD, Bertin A, Jalfre M (1977) Behavioural despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 229:327–336
Raiendra Prasad Y, Lakshmana Rao A, Prasoona L, Murali K, Ravi Kumar P (2005) Synthesis and antidepressant activity of some 1, 3, 5-triphenyl-2-pyrazolines and 3-(2″-hydroxy naphthalen-1″-yl)-1, 5-diphenyl-2-pyrazolines. Bioorg Med Chem Lett 15:5030–5034
Schäfer H (1985) Chemical constitution and pharmacological effect. In: Frey HH, Janz D (eds) Handbook of experimental pharmacology-antiepileptic drugs. Springer-Verlag, Berlin, chapter 9, pp 199–210
Schmid HH, Schmid PC, Natarajan V (1990) N-acylated glycerophospholipids and their derivatives. Prog Lipid Res 29:1–43
Van Heyningen E, Brown CN, José F, Henderson JK, Stark P (1966) N-monoalkyl-β-alkylcinnamamides as sedatives. J Med Chem 9:675–681
Willner P (1991) Animal models as stimulations of depression. Trends Pharmacol Sci 12:131–138
Acknowledgment
This study was supported by the National Natural Science Foundation of China (No. 30960458).
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Guan, LP., Sui, X., Deng, XQ. et al. N-palmitoylethanolamide derivatives: synthesis and studies on anticonvulsant and antidepressant activities. Med Chem Res 20, 601–606 (2011). https://doi.org/10.1007/s00044-010-9357-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00044-010-9357-7