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Alcoholism and alcohol use disorders are characterized by several months to decades of heavy and problematic drinking, interspersed with periods of abstinence and relapse to heavy drinking. This alcohol-drinking phenotype was modeled using macaque monkeys to explore neuronal adaptations in the striatum, a brain region controlling habitual behaviors. Prolonged drinking with repeated abstinence narrowed the variability in daily intake, increased the amount of ethanol consumed in bouts, and led to higher blood ethanol concentrations more than twice the legal intoxication limit. After the final abstinence period of this extensive drinking protocol, we found a selective increase in dendritic spine density and enhanced glutamatergic transmission in the putamen, but not in the caudate nucleus. Intrinsic excitability of medium-sized spiny neurons was also enhanced in the putamen of alcohol-drinking monkeys in comparison with non-drinkers, and GABAeric transmission was selectively suppressed in the putamen of heavy drinkers. These morphological and physiological changes indicate a shift in the balance of inhibitory/excitatory transmission that biases the circuit toward an enduring increase in synaptic activation of putamen output as a consequence of prolonged heavy drinking/relapse. The resultant potential for increased putamen activation may underlie an alcohol-drinking phenotype of regulated drinking and sustained intoxication.

Alcoholism and alcohol use disorders are characterized by several months to decades of heavy and problematic drinking, interspersed with periods of abstinence and relapse to heavy drinking. This alcohol-drinking phenotype was modeled using macaque monkeys to explore neuronal adaptations in the striatum, a brain region controlling habitual behaviors. Prolonged drinking with repeated abstinence narrowed the variability in daily intake, increased the amount of ethanol consumed in bouts, and led to higher blood ethanol concentrations more than twice the legal intoxication limit. After the final abstinence period of this extensive drinking protocol, we found a selective increase in dendritic spine density and enhanced glutamatergic transmission in the putamen, but not in the caudate nucleus. Intrinsic excitability of medium-sized spiny neurons was also enhanced in the putamen of alcohol-drinking monkeys in comparison with non-drinkers, and GABAeric transmission was selectively suppressed in the putamen of heavy drinkers. These morphological and physiological changes indicate a shift in the balance of inhibitory/excitatory transmission that biases the circuit toward an enduring increase in synaptic activation of putamen output as a consequence of prolonged heavy drinking/relapse. The resultant potential for increased putamen activation may underlie an alcohol-drinking phenotype of regulated drinking and sustained intoxication.

The role of positive vs negative ethanol reinforcement in ethanol intake of Sardinian alcohol-preferring (sP) rats is unclear.To test the hypothesis that spontaneous ethanol self-administration of sP rats was sensitive to the opioid receptor antagonist naltrexone, whereas withdrawal-induced, but not spontaneous, ethanol self-administration would be sensitive to corticotropin-releasing factor(1) (CRF(1)) antagonists, implicating differential roles for positive and negative reinforcement, respectively.Male sP rats operantly (FR1, 30 min/day) self-administered ethanol (10% v/v) until responding stabilized. One group (n=11) was made ethanol dependent through intermittent ethanol vapor exposure. Both nondependent (n = 10) and dependent rats received the CRF(1) antagonist LWH-63 (5, 10, and 20 mg/kg, s.c.). Separate nondependent sP rats (n = 10) received the opioid antagonist naltrexone (16, 50, 150, and 450 microg/kg, s.c.). Finally, CRF(1) antagonists (MJL-1-109-2, LWH-63, and R121919) were studied for their actions on home-cage ethanol drinking in nondependent sP rats (n = 6-8/group) under continuous, limited-access, or stressed conditions.Naltrexone potently reduced ethanol self-administration in nondependent sP rats. LWH-63 reduced heightened ethanol self-administration of vapor-sensitive, dependent sP rats. CRF(1) antagonists did not reduce ethanol intake in nondependent sP rats. R121919 (10 mg/kg, s.c.) retained antistress activity in sP rats, blunting novelty stress-induced suppression of ethanol intake.Spontaneous ethanol self-administration of sP rats was opioid dependent with CRF(1) receptors implicated in withdrawal-induced drinking. Opioid and CRF(1) receptors play different roles in ethanol reinforcement and perhaps the ethanol addiction cycle. Such distinctions may apply to subtypes of alcoholic patients who differ in their motivation to drink and ultimately treatment response.

The role of positive vs negative ethanol reinforcement in ethanol intake of Sardinian alcohol-preferring (sP) rats is unclear.To test the hypothesis that spontaneous ethanol self-administration of sP rats was sensitive to the opioid receptor antagonist naltrexone, whereas withdrawal-induced, but not spontaneous, ethanol self-administration would be sensitive to corticotropin-releasing factor(1) (CRF(1)) antagonists, implicating differential roles for positive and negative reinforcement, respectively.Male sP rats operantly (FR1, 30 min/day) self-administered ethanol (10% v/v) until responding stabilized. One group (n=11) was made ethanol dependent through intermittent ethanol vapor exposure. Both nondependent (n = 10) and dependent rats received the CRF(1) antagonist LWH-63 (5, 10, and 20 mg/kg, s.c.). Separate nondependent sP rats (n = 10) received the opioid antagonist naltrexone (16, 50, 150, and 450 microg/kg, s.c.). Finally, CRF(1) antagonists (MJL-1-109-2, LWH-63, and R121919) were studied for their actions on home-cage ethanol drinking in nondependent sP rats (n = 6-8/group) under continuous, limited-access, or stressed conditions.Naltrexone potently reduced ethanol self-administration in nondependent sP rats. LWH-63 reduced heightened ethanol self-administration of vapor-sensitive, dependent sP rats. CRF(1) antagonists did not reduce ethanol intake in nondependent sP rats. R121919 (10 mg/kg, s.c.) retained antistress activity in sP rats, blunting novelty stress-induced suppression of ethanol intake.Spontaneous ethanol self-administration of sP rats was opioid dependent with CRF(1) receptors implicated in withdrawal-induced drinking. Opioid and CRF(1) receptors play different roles in ethanol reinforcement and perhaps the ethanol addiction cycle. Such distinctions may apply to subtypes of alcoholic patients who differ in their motivation to drink and ultimately treatment response.

Objectif : synthétiser et caractériser des dérivés de 2-(1H-indol-3-ylméthyl) -1,3,4- oxadiazole-5-thiol S-alkylés/aralkylés. Méthodes : L'acide 2-(1H-indol-3-yl)acétique (1) a été mis à réagir avec de l'éthanol absolu et une quantité catalytique d'acide sulfurique pour former du 2-(1H-indol-3-yl)acétate d'éthyle (2) qui a été transformé en 2-(1H-indol-3-yl)acétohydrazide (3) par reflux avec de l'hydrate d'hydrazine dans du méthanol. La réaction de fermeture de cycle de 3 avec le disulfure de carbone et l'hydroxyde de potassium éthanolique a donné le 2-(1H-indol-3-ylméthyl) -1,3,4-oxadiazole-5-thiol (4) qui a finalement été traité avec des halogénures d'alkyle/aralkyle (5a-u) dans le DMF et le NaH pour donner des 2-(1H-indol-3-ylméthyl) -1,3,4-oxadiazole-5-thiols salkylés/ aralkylés (6a-u). L'élucidation structurelle a été réalisée par les techniques IR, 1H-NMR et EI-MSRésultats : le 2-(1H-indol-3-ylméthyl) -1,3,4-oxadiazole-5-thiol (4) a été synthétisé comme molécule mère et a été caractérisé par IR et le spectre a montré des pics résonnant à (cm-1) 2925 (Ar-H), 2250 (S-H ), 1593 (C=N ) et 1527 (Ar C=C ) ; le spectre 1H-NMR a montré des signaux à δ 11,00 (s, 1H, NH-1 ′), 7,49 (br.d, J = 7,6 Hz, 1H, H-4'), 7,37 (br.d, J = 8,0 Hz, 1H, H-7'), 7,34 (br.s, 1H, H-2'), 7,09 (t, J = 7,6 Hz, 1H, H-5'), 7,00 (t, J = 7,6 Hz, 1H, H-6') et 4,20 (s, 2H, CH2-10 ′). EI-MS présentait différents pics de fragments à m/z 233 (C11H9N3OS) + [M+2]+, 231 (C11H9N3OS) + [M]+, 158 (C10H8NO)+, 156 (C10H8N2) +, 130 (C9H8N)+. Les dérivés (6a-6u) ont été préparés et caractérisés en conséquence.Conclusion : 2-(1H-indol-3-ylméthyl) -1,3,4-oxadiazole-5-thiols (6a-u) S-alkylés/aralkylés ont été synthétisés avec succès.Mots clés : 2-(1H-indole-3-ylméthyl) -1,3,4-oxadiazole-5-thiol, dérivés S-alkylés/aralkylés, synthèse, caractérisation, 1H-RMN et EI-MS Propósito: Sintetizar y caracterizar derivados de 2-(1H-indol-3-ilmetil) -1,3,4-oxadiazol-5-tiol S-alquilados/aralquilados. Métodos: El ácido 2-(1H-indol-3-il)acético (1) se hizo reaccionar con etanol absoluto y una cantidad catalítica de ácido sulfúrico para formar 2-(1H-indol-3-il)acetato de etilo (2) que se transformó en 2-(1H-indol-3-il)acetohidrazida (3) calentando a reflujo con hidrato de hidrazina en metanol. La reacción de cierre de anillo de 3 con disulfuro de carbono e hidróxido de potasio etanólico proporcionó 2-(1H-indol-3-ilmetil) -1,3,4-oxadiazol-5-tiol (4) que finalmente se trató con haluros de alquilo/aralquilo (5a-u) en DMF y NaH para proporcionar 2-(1H-indol-3-ilmetil) -1,3,4-oxadiazol-5-tioles salquilados/ aralquilados (6a-u). La elucidación estructural se realizó mediante técnicas IR, 1H-NMR y EI-MS. Resultados: 2-(1H-indol-3-ilmetil) -1,3,4-oxadiazol-5-tiol (4) se sintetizó como la molécula original y se caracterizó mediante IR y el espectro mostró picos que resonaban a (cm-1) 2925 (Ar-H), 2250 (S-H ), 1593 (C=N ) y 1527 (Ar C=C ); el espectro de 1H-NMR mostró señales a δ 11.00 (s, 1H, NH-1 '), 7.49 ( br.d, J = 7.6 Hz, 1H, H-4'), 7.37 (br.d, J = 8.0 Hz, 1H, H-7 '), 7.34 (br.s, 1H, H-2'), 7.09 (t, J = 7.6Hz, 1H, H-5 '), 7.00 (t, J = 7.6 Hz, 1H, H-6') y 4.20 (s, 2H, CH2-10 '). La EI-MS presentó diferentes picos de fragmentos en m/z 233 (C11H9N3OS) + [M+2]+, 231 (C11H9N3OS) + [M]+, 158 (C10H8NO)+, 156 (C10H8N2)+, 130 (C9H8N)+. Los derivados (6a-6u) se prepararon y caracterizaron en consecuencia. Conclusión: 2-(1H-indol-3-ilmetil) -1,3,4-oxadiazol-5-tioles S-alquilados/aralquilados (6a-u) se sintetizaron con éxito. Palabras clave: 2-(1H-indol-3-ilmetil) -1,3,4-oxadiazol-5-tiol, derivados S-alquilados/aralquilados, síntesis, caracterización, 1H-NMR y EI-MS Purpose: To synthesize and characterize S-alkylated/aralkylated 2-(1H-indol-3-ylmethyl)-1,3,4- oxadiazole-5-thiol derivatives.Methods: 2-(1H-indol-3-yl)acetic acid (1) was reacted with absolute ethanol and catalytic amount of sulfuric acid to form ethyl 2-(1H-indol-3-yl)acetate (2) which was transformed to 2-(1H-indol-3- yl)acetohydrazide (3) by refluxing with hydrazine hydrate in methanol. Ring closure reaction of 3 with carbon disulfide and ethanolic potassium hydroxide yielded 2-(1H-indol-3-ylmethyl)-1,3,4-oxadiazole-5- thiol (4) which was finally treated with alkyl/aralkyl halides (5a-u) in DMF and NaH to yield Salkylated/ aralkylated 2-(1H-indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiols (6a-u). Structural elucidation was done by IR, 1H-NMR and EI-MS techniquesResults: 2-(1H-indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiol (4) was synthesized as the parent molecule and was characterized by IR and the spectrum showed peaks resonating at (cm-1) 2925 (Ar-H), 2250 (S-H ), 1593 (C=N ) and 1527 (Ar C=C ); 1H-NMR spectrum showed signals at δ 11.00 (s, 1H, NH-1ʹ), 7.49 ( br.d, J = 7.6 Hz, 1H, H-4'), 7.37 (br.d, J = 8.0 Hz, 1H, H-7'), 7.34 (br.s, 1H, H-2'), 7.09 (t, J = 7.6Hz, 1H, H-5'), 7.00 (t, J = 7.6 Hz, 1H, H-6') and 4.20 (s, 2H, CH2-10ʹ). EI-MS presented different fragments peaks at m/z 233 (C11H9N3OS)˙+ [M+2]+, 231 (C11H9N3OS)˙+ [M]+, 158 (C10H8NO)+, 156 (C10H8N2)˙+, 130 (C9H8N)+. The derivatives (6a-6u) were prepared and characterized accordingly.Conclusion: S-alkylated/aralkylated 2-(1H-indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiols (6a-u) were successfully synthesized.Keywords: 2-(1H-indole-3-ylmethyl)-1,3,4-oxadiazole-5-thiol, S-alkylated/aralkylated derivatives, Synthesis, Characterization, 1H-NMR and EI-MS الغرض: لتوليف وتوصيف مشتقات S - alkylated/aralkylated 2 -(1H -indol -3 - ylmethyl) -1,3,4 - oxadiazole -5 - thiol. الطرق: 2 -(1H - indol -3 - yl) تم تفاعل حمض الخليك (1) مع الإيثانول المطلق والكمية الحفازة من حمض الكبريتيك لتشكيل أسيتات الإيثيل 2 -(1H - indol -3 - yl) (2) التي تم تحويلها إلى 2 -(1H - indol -3 - yl)acetohydrazide (3) عن طريق الارتداد مع هيدرات الهيدرازين في الميثانول. أدى تفاعل إغلاق الحلقة 3 مع ثاني كبريتيد الكربون وهيدروكسيد البوتاسيوم الإيثانولي إلى 2 -(1H - indol -3 - ylmethyl) -1،3،4 - oxadiazole -5 - thiol (4) والذي تمت معالجته أخيرًا بهاليد الألكيل/الأركيل (5a - u) في DMF و NaH لإنتاج 2 - (1H - indol -3 - ylmethyl) -1،3،4 - oxadiazole -5 - thiols (6a - u). تم إجراء التوضيح الهيكلي بواسطة تقنيات الأشعة تحت الحمراء، 1H - NMR و EI - MSالنتائج: 2 - (1H - indol -3 - ylmethyl) -1،3،4 - oxadiazole -5 - thiol (4) تم توليفها كجزيء أصلي وتم تمييزها بالأشعة تحت الحمراء وأظهر الطيف قمم صدى عند (cm -1) 2925 (Ar - H)، 2250 (S - H)، 1593 (C=N) و 1527 (Ar C = C) ؛ أظهر طيف 1H - NMR إشارات عند δ 11.00 (s، 1H، NH -1 ')، 7.49 (br.d، J = 7.6 Hz، 1H، H -4 ')، 7.37 (br.d، J = 8.0 Hz، 1H، H -7 ')، 7.34 (br.s، 1H، H -2 ')، 7.09 (t، J = 7.6Hz، 1H، H -5 ')، 7.00 (t = J.6 Hz، 1-6 Hh) و 4.20 (s، 2H، CH -102). قدم EI - MS قمم شظايا مختلفة عند m/z 233 (C11H9N3OS) + [M+2]+، 231 (C11H9N3OS) + [M]+، 158 (C10H8NO)+، 156 (C10H8N2) +، 130 (C9H8N)+. تم إعداد المشتقات (6a -6u) وتمييزها وفقًا لذلك. الخاتمة: S - alkylated/aralkylated 2 -(1H - indol -3 - ylmethyl) -1،3،4 - oxadiazole -5 - thiols (6a - u) تم تصنيعها بنجاح. الكلمات الرئيسية: 2 -(1H - indole -3 - ylmethyl)-1،3،4 - oxadiazole -5 - thiol، S - alkylated/aralkylated derivatives، Synthesis، Characterization، 1H - NMR و EI - MS

Objectif : synthétiser et caractériser des dérivés de 2-(1H-indol-3-ylméthyl) -1,3,4- oxadiazole-5-thiol S-alkylés/aralkylés. Méthodes : L'acide 2-(1H-indol-3-yl)acétique (1) a été mis à réagir avec de l'éthanol absolu et une quantité catalytique d'acide sulfurique pour former du 2-(1H-indol-3-yl)acétate d'éthyle (2) qui a été transformé en 2-(1H-indol-3-yl)acétohydrazide (3) par reflux avec de l'hydrate d'hydrazine dans du méthanol. La réaction de fermeture de cycle de 3 avec le disulfure de carbone et l'hydroxyde de potassium éthanolique a donné le 2-(1H-indol-3-ylméthyl) -1,3,4-oxadiazole-5-thiol (4) qui a finalement été traité avec des halogénures d'alkyle/aralkyle (5a-u) dans le DMF et le NaH pour donner des 2-(1H-indol-3-ylméthyl) -1,3,4-oxadiazole-5-thiols salkylés/ aralkylés (6a-u). L'élucidation structurelle a été réalisée par les techniques IR, 1H-NMR et EI-MSRésultats : le 2-(1H-indol-3-ylméthyl) -1,3,4-oxadiazole-5-thiol (4) a été synthétisé comme molécule mère et a été caractérisé par IR et le spectre a montré des pics résonnant à (cm-1) 2925 (Ar-H), 2250 (S-H ), 1593 (C=N ) et 1527 (Ar C=C ) ; le spectre 1H-NMR a montré des signaux à δ 11,00 (s, 1H, NH-1 ′), 7,49 (br.d, J = 7,6 Hz, 1H, H-4'), 7,37 (br.d, J = 8,0 Hz, 1H, H-7'), 7,34 (br.s, 1H, H-2'), 7,09 (t, J = 7,6 Hz, 1H, H-5'), 7,00 (t, J = 7,6 Hz, 1H, H-6') et 4,20 (s, 2H, CH2-10 ′). EI-MS présentait différents pics de fragments à m/z 233 (C11H9N3OS) + [M+2]+, 231 (C11H9N3OS) + [M]+, 158 (C10H8NO)+, 156 (C10H8N2) +, 130 (C9H8N)+. Les dérivés (6a-6u) ont été préparés et caractérisés en conséquence.Conclusion : 2-(1H-indol-3-ylméthyl) -1,3,4-oxadiazole-5-thiols (6a-u) S-alkylés/aralkylés ont été synthétisés avec succès.Mots clés : 2-(1H-indole-3-ylméthyl) -1,3,4-oxadiazole-5-thiol, dérivés S-alkylés/aralkylés, synthèse, caractérisation, 1H-RMN et EI-MS Propósito: Sintetizar y caracterizar derivados de 2-(1H-indol-3-ilmetil) -1,3,4-oxadiazol-5-tiol S-alquilados/aralquilados. Métodos: El ácido 2-(1H-indol-3-il)acético (1) se hizo reaccionar con etanol absoluto y una cantidad catalítica de ácido sulfúrico para formar 2-(1H-indol-3-il)acetato de etilo (2) que se transformó en 2-(1H-indol-3-il)acetohidrazida (3) calentando a reflujo con hidrato de hidrazina en metanol. La reacción de cierre de anillo de 3 con disulfuro de carbono e hidróxido de potasio etanólico proporcionó 2-(1H-indol-3-ilmetil) -1,3,4-oxadiazol-5-tiol (4) que finalmente se trató con haluros de alquilo/aralquilo (5a-u) en DMF y NaH para proporcionar 2-(1H-indol-3-ilmetil) -1,3,4-oxadiazol-5-tioles salquilados/ aralquilados (6a-u). La elucidación estructural se realizó mediante técnicas IR, 1H-NMR y EI-MS. Resultados: 2-(1H-indol-3-ilmetil) -1,3,4-oxadiazol-5-tiol (4) se sintetizó como la molécula original y se caracterizó mediante IR y el espectro mostró picos que resonaban a (cm-1) 2925 (Ar-H), 2250 (S-H ), 1593 (C=N ) y 1527 (Ar C=C ); el espectro de 1H-NMR mostró señales a δ 11.00 (s, 1H, NH-1 '), 7.49 ( br.d, J = 7.6 Hz, 1H, H-4'), 7.37 (br.d, J = 8.0 Hz, 1H, H-7 '), 7.34 (br.s, 1H, H-2'), 7.09 (t, J = 7.6Hz, 1H, H-5 '), 7.00 (t, J = 7.6 Hz, 1H, H-6') y 4.20 (s, 2H, CH2-10 '). La EI-MS presentó diferentes picos de fragmentos en m/z 233 (C11H9N3OS) + [M+2]+, 231 (C11H9N3OS) + [M]+, 158 (C10H8NO)+, 156 (C10H8N2)+, 130 (C9H8N)+. Los derivados (6a-6u) se prepararon y caracterizaron en consecuencia. Conclusión: 2-(1H-indol-3-ilmetil) -1,3,4-oxadiazol-5-tioles S-alquilados/aralquilados (6a-u) se sintetizaron con éxito. Palabras clave: 2-(1H-indol-3-ilmetil) -1,3,4-oxadiazol-5-tiol, derivados S-alquilados/aralquilados, síntesis, caracterización, 1H-NMR y EI-MS Purpose: To synthesize and characterize S-alkylated/aralkylated 2-(1H-indol-3-ylmethyl)-1,3,4- oxadiazole-5-thiol derivatives.Methods: 2-(1H-indol-3-yl)acetic acid (1) was reacted with absolute ethanol and catalytic amount of sulfuric acid to form ethyl 2-(1H-indol-3-yl)acetate (2) which was transformed to 2-(1H-indol-3- yl)acetohydrazide (3) by refluxing with hydrazine hydrate in methanol. Ring closure reaction of 3 with carbon disulfide and ethanolic potassium hydroxide yielded 2-(1H-indol-3-ylmethyl)-1,3,4-oxadiazole-5- thiol (4) which was finally treated with alkyl/aralkyl halides (5a-u) in DMF and NaH to yield Salkylated/ aralkylated 2-(1H-indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiols (6a-u). Structural elucidation was done by IR, 1H-NMR and EI-MS techniquesResults: 2-(1H-indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiol (4) was synthesized as the parent molecule and was characterized by IR and the spectrum showed peaks resonating at (cm-1) 2925 (Ar-H), 2250 (S-H ), 1593 (C=N ) and 1527 (Ar C=C ); 1H-NMR spectrum showed signals at δ 11.00 (s, 1H, NH-1ʹ), 7.49 ( br.d, J = 7.6 Hz, 1H, H-4'), 7.37 (br.d, J = 8.0 Hz, 1H, H-7'), 7.34 (br.s, 1H, H-2'), 7.09 (t, J = 7.6Hz, 1H, H-5'), 7.00 (t, J = 7.6 Hz, 1H, H-6') and 4.20 (s, 2H, CH2-10ʹ). EI-MS presented different fragments peaks at m/z 233 (C11H9N3OS)˙+ [M+2]+, 231 (C11H9N3OS)˙+ [M]+, 158 (C10H8NO)+, 156 (C10H8N2)˙+, 130 (C9H8N)+. The derivatives (6a-6u) were prepared and characterized accordingly.Conclusion: S-alkylated/aralkylated 2-(1H-indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiols (6a-u) were successfully synthesized.Keywords: 2-(1H-indole-3-ylmethyl)-1,3,4-oxadiazole-5-thiol, S-alkylated/aralkylated derivatives, Synthesis, Characterization, 1H-NMR and EI-MS الغرض: لتوليف وتوصيف مشتقات S - alkylated/aralkylated 2 -(1H -indol -3 - ylmethyl) -1,3,4 - oxadiazole -5 - thiol. الطرق: 2 -(1H - indol -3 - yl) تم تفاعل حمض الخليك (1) مع الإيثانول المطلق والكمية الحفازة من حمض الكبريتيك لتشكيل أسيتات الإيثيل 2 -(1H - indol -3 - yl) (2) التي تم تحويلها إلى 2 -(1H - indol -3 - yl)acetohydrazide (3) عن طريق الارتداد مع هيدرات الهيدرازين في الميثانول. أدى تفاعل إغلاق الحلقة 3 مع ثاني كبريتيد الكربون وهيدروكسيد البوتاسيوم الإيثانولي إلى 2 -(1H - indol -3 - ylmethyl) -1،3،4 - oxadiazole -5 - thiol (4) والذي تمت معالجته أخيرًا بهاليد الألكيل/الأركيل (5a - u) في DMF و NaH لإنتاج 2 - (1H - indol -3 - ylmethyl) -1،3،4 - oxadiazole -5 - thiols (6a - u). تم إجراء التوضيح الهيكلي بواسطة تقنيات الأشعة تحت الحمراء، 1H - NMR و EI - MSالنتائج: 2 - (1H - indol -3 - ylmethyl) -1،3،4 - oxadiazole -5 - thiol (4) تم توليفها كجزيء أصلي وتم تمييزها بالأشعة تحت الحمراء وأظهر الطيف قمم صدى عند (cm -1) 2925 (Ar - H)، 2250 (S - H)، 1593 (C=N) و 1527 (Ar C = C) ؛ أظهر طيف 1H - NMR إشارات عند δ 11.00 (s، 1H، NH -1 ')، 7.49 (br.d، J = 7.6 Hz، 1H، H -4 ')، 7.37 (br.d، J = 8.0 Hz، 1H، H -7 ')، 7.34 (br.s، 1H، H -2 ')، 7.09 (t، J = 7.6Hz، 1H، H -5 ')، 7.00 (t = J.6 Hz، 1-6 Hh) و 4.20 (s، 2H، CH -102). قدم EI - MS قمم شظايا مختلفة عند m/z 233 (C11H9N3OS) + [M+2]+، 231 (C11H9N3OS) + [M]+، 158 (C10H8NO)+، 156 (C10H8N2) +، 130 (C9H8N)+. تم إعداد المشتقات (6a -6u) وتمييزها وفقًا لذلك. الخاتمة: S - alkylated/aralkylated 2 -(1H - indol -3 - ylmethyl) -1،3،4 - oxadiazole -5 - thiols (6a - u) تم تصنيعها بنجاح. الكلمات الرئيسية: 2 -(1H - indole -3 - ylmethyl)-1،3،4 - oxadiazole -5 - thiol، S - alkylated/aralkylated derivatives، Synthesis، Characterization، 1H - NMR و EI - MS

The effects of alcohol and other psychotropic drugs on eye movements are reviewed with particular attention to the possible relevance of these effects for traffic safety. Alcohol has been shown to have diverse effects, including reduction of the velocity of both saccadic and smooth pursuit eye movements, increased saccadic latency, impairment of convergence and induction of nystagmus. These effects probably contribute to impaired visual information processing, which reduces driving ability. Barbiturates have been reported to produce effects similar to alcohol, and the effects of benzodiazepines and opioids seem to be more limited but still substantial. Marihuana has relatively little effect on eye movements.

The effects of alcohol and other psychotropic drugs on eye movements are reviewed with particular attention to the possible relevance of these effects for traffic safety. Alcohol has been shown to have diverse effects, including reduction of the velocity of both saccadic and smooth pursuit eye movements, increased saccadic latency, impairment of convergence and induction of nystagmus. These effects probably contribute to impaired visual information processing, which reduces driving ability. Barbiturates have been reported to produce effects similar to alcohol, and the effects of benzodiazepines and opioids seem to be more limited but still substantial. Marihuana has relatively little effect on eye movements.