Receptor Antagonist, N-n- propyl-3-ethoxyquinoxaline-2-carboxamide (6n)

Transcription

1 Pharmacology Antidepressant Potential of 5-HT 3 Receptor Antagonist, -n- propyl-3-ethoxyquinoxaline-2-carboxamide (6n) Mahesh R, Bhatt S, Devadoss T, Jindal AK, Gautam BK, Pandey DK Department of Pharmacy, FD-III, Birla Institute of Technology and Science, Pilani, Rajasthan, India Address for correspondence: Mr. Shvetank Bhatt, shvetankbhatt@gmail.com ABSTRACT A 2 value Key words: 3 receptor antagonists, forced swim test, head twitch, reserpine, tail suspension test ITRDUCTI population across the globe. It is one of the top ten Quick Response Code: Access this article online Website: DI: 1.413/ Journal of Young Pharmacists Vol 4 / o 4 235

2 Mahesh, et al.: Antidepressant potential of -n-propyl-3-ethoxyquinoxaline-2-carboxamide (6n) receptors in the chemoreceptor receptor antagonists, vomiting. receptor antagonists, their receptors in the central disorders. Studies on human beings using selective receptor antagonists discovered heterogeneous e.g., nucleus tractus solitarius, area postrema, and caudate. Evidence for the relevance receptor antagonists in the treatment of depression. receptor antagonism in 1B 2A, in various behavioral and mechanistic rodent models of antagonist receptor in isolated guinea pig ileum, and the pa 2 drug. compounds. Evaluation of chronic effect to provide significant information on A 2 and log P values. A 2 values (pa 2 receptor antagonist, A2 antidepressant screening in the standard rodent models of depression as mentioned above. P and pa2 values of series of 3-ethoxyquinoxali-2-carboxamides 6a-6q H R 7 Compound R Log P a b pa 2 6a C 6 H b 4-Me-C 6 H c 4-Me-C 6 H d C 6 H 5 -CH e C 6 H 5 -H f 3-Ac-C 6 H n 3-Cl-C 6 H h 4-2 -C 6 H i 2-pyridinyl j 3-Cl-2-CH 3 -C 6 H k Benzothiazol-2-yl l 4-Benzamido-phenyl m 2-Benzamido-phenyl n CH3CH2CH o CH 3 CH 2 CH 2 CH Pyrrolidinyl p Cyclopentyl q Cyclohexyl ndansetron a logp values were calculated using ChemBioDraw Ultra 11 (Cambridge Software) b pa 2 values are the means of two separate experiments. SE was less than 1% of the mean R 236 Journal of Young Pharmacists Vol 4 / o 4

3 Mahesh, et al.: Antidepressant potential of -n-propyl-3-ethoxyquinoxaline-2-carboxamide (6n) Animals MATERIALS AD METHDS ad libitum. Behavioral each experiment. Chemistry of 6n receptor antagonists Drugs and chemicals 5-HT 3 receptor antagonistic activity the pa 2 H 2 a C 2 H 5 b C 2 H 5 H 2 1 H 2 3 Cl c,d H f,g H e H 6n 5 4 Cl Figure 1: 3 3 CH 3 Journal of Young Pharmacists Vol 4 / o 4 237

4 Mahesh, et al.: Antidepressant potential of -n-propyl-3-ethoxyquinoxaline-2-carboxamide (6n) Spontaneous locomotor activity Figure 2: 3 receptor antagonists antagonist effect of the test compounds on the response A 2 A 2 values Forced swim test before the test. Tail suspension test an actophotometer. 5-hydroxytryptophan-induced head twitch response glass cages (12 12 Interaction studies in forced swim test and tail suspension test All the and standard responses recorded. Reserpine-induced hypothermia in rats th minute values 238 Journal of Young Pharmacists Vol 4 / o 4

5 Mahesh, et al.: Antidepressant potential of -n-propyl-3-ethoxyquinoxaline-2-carboxamide (6n) similar manner in order to habituate the animals to the experimental procedures. lfactory bulbectomy described earlier. to bregma and 2 mm on either side of the midline at a point corresponding to the posterior margin of the orbit pen eld test behavior th Statistical analysis post-hoc Dunnett s test post-hoc P RESULTS Based on the pa 2 and log P from amongst the series of compounds. (P n (mg/kg) ESC Figure 3: Effect of 6n on duration of immobility of mice FST. The columns represent mean duration of immobility in seconds (s) and error bars indicate S.D. n = 8 per group. P<.5 compared with vehicle treated group. # P<.5, ESC compared with 1 mg/kg treatment group. ESC = Escitalopram # Journal of Young Pharmacists Vol 4 / o 4 239

6 ahesh.: Antidepressant potential of -n-propyl-3-ethoxyquinoxaline-2-carboxamide (6n) a significant (P P For a conclusive evaluation of antidepressant potential n (mg/kg) BUP Figure 4: Effect of 6n on duration of immobility of mice TST. The columns represent mean duration of immobility in seconds (s) and error bars indicate S.D. n = 8 per group. P<.5 compared with vehicle treated group. # P $ P # Locomotor scores n (mg/kg) Figure 5: Effect of 6n on spontaneous locomotor activity of mice. The columns represent mean locomotor scores recorded in a 1-minute observation period. The error bars indicate S.D., n = 8 per group Mean decrease in temperature ( F) mber of head twitches n (mg/kg) FLX 6n (mg/kg) ESC Figure 6: Effect of 6n on reserpine-induced hypothermia in rats. The indicate S.D. n = 8 per group. P<.5 compared with vehicle-treated group. ESC = Escitalopram Figure 7: mg/kg) + pargyline (75 mg/kg)-induced head twitch response in mice. The columns represent mean number of head twitches and error bars indicate S.D. n = 8 per group. P<.5 compared with vehicle-treated 24 Journal of Young Pharmacists Vol 4 / o 4

7 Mahesh, et al.: Antidepressant potential of -n-propyl-3-ethoxyquinoxaline-2-carboxamide (6n) P DISCUSSI receptor. receptors are expressed in nucleus tractussolitarius, area postrema, and spinal trigeminal nucleus nucleus accumbens, putamen, caudate indicate their role in as the areas mentioned affected in # FLX 6n (1) + FLX #$ Duration of immobility(s) # VLA 6n (1) + VLA #$ Dose (mg/kg ) Dose (mg/kg) Figure 8: Effect of 6n of immobility (s) and error bars indicate S.D., n = 8 per group. P<.5 compared with vehicle-treated group. # P $ P<.5 compared with 6n treated group Figure 9: Effect of 6n (1 mg/kg) on antidepressant activity of venlafaxine (VLA) in mice FST. The columns represent mean duration of immobility (s) and error bars indicate S.D. n = 8 per group. P<.5 compared with vehicle-treated group. # P 8 mg/ kg) treated group. $ P<.5 compared with 6n-treated group # 6n 6n + Harmane (5) #$ # 6n 6n + PT (1) # 1 2 Dose (mg/kg) 1 2 Dose (mg/kg) Figure 1: Effect of 6n Harmane (5 mg/kg) in mice FST. The columns represent mean duration of immobility in seconds (s) and error bars indicate S.D. n = 8 per group. P<.5 vs. vehicle treated Group. # P<.5 compared with 6n treated group. $ P<.5 compared vs harmane (5 mg/kg)-treated group Figure 11: Effect of 6n parthenolide (PT) in mice FST. The columns represent mean duration of immobility in seconds (s) and error bars indicate S.D. n = 8 per group. P<.5 vs vehicle-treated group. # P<.5 compared with PT (1 mg/kg)-treated group Journal of Young Pharmacists Vol 4 / o 4 241

8 ahesh.: Antidepressant potential of -n-propyl-3-ethoxyquinoxaline-2-carboxamide (6n) Figure 12: Effect of 6n (1 mg/kg) on antidepressant activity of bupropion in seconds (s) and error bars indicate S.D., n = 8 per group. P<.5 vs vehicle-treated group. # P<.5 compared with bupropion (1 and $ P<.5 compared with 6n-treated group Treatment Ambulation score Rearing score Fecal pellet Sham Control ± ± ±.23 Sham+6n (1) 13. ± ± ±.87 Sham+6n (2) ± ± ±.89 Sham+Par (1) ± ± ±.81 BX Control 225 ± ± ±.92 BX+6n (1) 14. ± 1.82 # 15. ± 2.1 # 3.8 ±.92 # BX+6n (2) 138 ± # 11.4 ± 2.18 # 3.67 ±.97 # BX+Par (1) 113 ± # ± 1.43 # 2.33 ±.99 # The value represent ambulation score, rearing score, and number of fecal pellet and error bars indicate S.D., P<.5 when compared with the sham-operated rats, # P<.5 when compared with the vehicle-treated BX rats (n = 8 per group) # 1 2 Dose (mg/kg) BUP 6n (1) + BUP #$ - For a conclusive evaluation of antidepressant potential carried out. alone treatment group. that produces antidepressants acting through serotonergic mechanisms. depression. could be due to the release of dopamine through inhibition receptors. and used to explore the antidepressant potential of novel 242 Journal of Young Pharmacists Vol 4 / o 4

9 Mahesh, et al.: Antidepressant potential of -n-propyl-3-ethoxyquinoxaline-2-carboxamide (6n) agents. environment. Moreover, other possible reason for habituate to novel environment. antagonist, the concentration of monoamine neurotransmitter via serotonergic modulation. CCLUSI locomotion of rodents at test receptor antagonism. ACKWLEDGMETS drug sample in short notice. REFERECES. et al reeptor antagonist, in animal models of Journal of Young Pharmacists Vol 4 / o 4 243

10 ahesh.: Antidepressant potential of -n-propyl-3-ethoxyquinoxaline-2-carboxamide (6n) pa2. et al et al How to cite this article: 3 receptor antagonist, - Source of Support: of Interest: one declared. Author Help: Reference checking facility The manuscript system ( allows the authors to check and verify the accuracy and style of references. The tool checks the references with PubMed as per a predefined style. Authors are encouraged to use this facility, before submitting articles to the journal. The style as well as bibliographic elements should be 1% accurate, to help get the references verified from the system. Even a single spelling error or addition of issue number/month of publication will lead to an error when verifying the reference. Example of a correct style Sheahan P, leary G, Lee G, Fitzgibbon J. Cystic cervical metastases: Incidence and diagnosis using fine needle aspiration biopsy. tolaryngol Head eck Surg 22;127: nly the references from journals indexed in PubMed will be checked. Enter each reference in new line, without a serial number. Add up to a maximum of 15 references at a time. If the reference is correct for its bibliographic elements and punctuations, it will be shown as CRRECT and a link to the correct article in PubMed will be given. If any of the bibliographic elements are missing, incorrect or extra (such as issue number), it will be shown as ICRRECT and link to possible articles in PubMed will be given. 244 Journal of Young Pharmacists Vol 4 / o 4