اردو اور ہندی کا لسانی اشتراک و افتراق

اردو اور ہندی کا لسانی اشتراک و افتراق Initially was only language used to express human ideas. In every age, along with customs and traditions, language also went through stages of evaluation. That is why language of each region is unique. This uniqueness of languages is of its identity. Like human beings, languages also have their own families, and different languages grow as sub- branches of language family. They flourish and sometimes thrive and come to life through process of evolution. When some languages die out. Urdu and Hindi also belong to large languages families. They have a deep relationship. And speaking of same relationship, some tinkers do not separate them from each other. When it sometimes thinkers, there is difference between in the two. At a glance, we will mention the linguistic similarities and difference between Urdu and Hindi. Where are places and where there is difference between them, but all of them are mentioned here.

Synthesis and Pharmacological Profiling of Gabapentin and Pregabalin Derivatives As Potential Therapeutic Agents in the Treatment of Neuropathic Pain

The present work describes the synthesis and pharmacological evaluation of gabapentin (GBP) and pregabalin (PGB) derivatives as potential therapeutic agents for the treatment of neuropathic pain. Synthesis of novel molecules for the treatment of different disease conditions has long been a strategy of the synthetic chemists. Organic synthesis utilizes the fundamental approach for the development of active molecules utilizing the hypothesis that the active molecules bind to an active site of enzymes or proteins with the subsequent response in the shape of a distinct biological activity. Chemically modifying the active molecule might result in an increase, decline or modification of the biological activity. From this basic thought, a panoptic range of dissimilar structures can be derived, extending to the development of superior and more efficient therapeutic agents. The hypothesis of modifying the structures of the PGB and GBP in an attempt to obtain newer molecules for the treatment of neuropathic pain with higher therapeutic potential, safety, and lesser side effects (as associated with the currently available treatments of neuropathic pain), persuaded us to chemically change their structures by incorporating salicylaldehyde moiety at their amine functionality. Neuropathic pain, the pain that originates from neuronal damage, is a chronic and enfeebling condition that imparts a lot of distress to the patients suffering from it. A number of studies have revealed a potential effectiveness of opioids, tricyclic antidepressants (TCAs), mexilitine, tramadol, and anticonvulsants like PGB, GBP, phenytoin, and lamotrigine for painful neuropathic conditions. Nevertheless, all these therapies only have an effectiveness rate of 30-50 percent in reducing pain and are treatment with these agents is stopped due to serious side effects, sedation being the most common.PGB and GBP are amino acids with anticonvulsant, analgesic and anxiolytic like activities. PGB was intended as a lipophilic analogue of GABA and was substituted at 3 position in order to assist its passage across the blood brain barrier (BBB). On the other hand, GBP was developed initially for the treatment of partial seizures (as add on therapy) but it was found to have effects in the treatment of post herpetic neuralgia (PHN) in various neuropathic preclinical pain models. The gabapentinoid anticonvulsants, PGB and GBP, have established efficacy in both preclinical and clinical neuropathic and chronic cancer pain research. PGB and GBP, though are the GABA analogues, but have a distinct mechanism of action than that of GABA. They act on the α2δ1 subunit of voltage gated calcium channels whereas GABA acts either on GABAA, GABAB or GABAC receptors. GBP has been utilized for the treatment of a range of neuropathic pain, anxiety, inflammation and in a number of other conditions. Similarly, the effectiveness of PGB in these conditions is well documented. After synthesis of PGB and GBP derivatives and their chemical characterization utilizing various analytical tools like 1H NMR, 13C NMR, IR, UV, and MS, these derivative were evaluated by employing various pharmacological assays. Following the synthesis and characterization of these compounds (PGS and GPS), acute toxicity study was undertaken to institute the safety windows. In the third phase, after synthesis and toxicological study, these derivatives were then tested inthe preliminary paradigms of nociception (hot plate and abdominal stretch tests in mice), inflammation (carrageenan, histamine, and serotonin induced paw edema models in mice) , and pyrexia (Brewer''s yeast induced pyrexia model in mice) where they showed significant antinociceptive, anti-inflammatory, and antipyretic proclivities. The antinociceptive effects of PGS and GPS in abdominal stretch test were ostensibly antagonized naloxone, while the antinociceptive effects of these compounds in the hot plate test were preferentially antagonized by naloxone (1 mg/kg, s.c) and pentylenetetrazole (PTZ) (15 mg/kg, i.p). The promising results from antinociceptive, anti-inflammatory, and antipyretic assays intrigued us to evaluate these compounds for their antiallodynic and antihyperalgesic potential in various neuropathic pain models including diabetes-induced (disease induced), chemotherapy-induced (treatment-induced) and chronic constriction injury induced (surgically-induced) neuropathic pain using either von Frey filament or cotton bud stimuli. In case of diabetes induced neuropathy model, antivulvodynic effects of these compounds were also evaluated. Here, hyperglycemia was induced via single injection of streptozotocin (45 mg/kg). PGS (30, 50, 75, and 100 mg/kg) and GPS (25, 50, 75 and 100 mg/kg) showed static/dynamic anti-allodynic [(increased paw withdrawal threshold (PWT) and latency (PWL)] in addition to static/dynamic anti-vulvodynia effects [increased flinching response threshold (FRT) and latency (FRL)], when compared to the positive controls, PGB (30 mg/kg) and GBP (100 mg/kg), and the vehicle control groups. The encouraging results from the STZ induced diabetic neuropathic pain model further enchanted us to evaluate these compounds in a chemotherapy induced peripheral neuropathy model (CIPN) in rats and also in chronic constriction injury (CCI) model of neuropathic pain. In CIPN model, both PGS (30, 50, 75, and 100 mg/kg) and GPS (25, 50, 75, and 100 mg/kg), demonstrated a significant effect in the amelioration of cisplatin (3.0 mg/kg, i.p) induced thermohypoalgesia and allodynia. Thermohypoalgesia attenuating potential of these compound imply an involvement of TRP channels which are specifically associated with thermo-perception. On the other hand, the promising results from the CCI model revealed that PGS and GPS possess significant ameliorating effects on suppressing of the neuropathic pain symptoms like mechanical allodynia, mechanical hyperalgesia, thermal hyperalgesia, and cold allodynia. Chronic pain and anxiety have a deep connection and keeping this in view, anxiolytic activity of PGS and GPS was evaluated in open-field, staircase, and elevated plus-maze tests. Bothe PGS and GPS produced anxiolytic-like effects at the tested doses that were evident in the open-field epitome from an increased time spent in the centre and no effect on the locomotor activity at all the tested doses, except for 100 mg/kg GPS dose where a mild decrease in locomotion was observed. PGS and GPS decreased the rearing incidence without suppressing the NSA in the staircase test. They also increased the number of entries to and time spent on open arms / central platform, respectively, as well as the frequency of head-dipping in the mouse elevated plus-maze assay. PTZ (15 mg/kg), a non-selective GABA antagonist, preferentially antagonized all these effects produced by PGS and GPS. In conclusion, PGS and GPS revealed promising anti-nociceptive, anti-inflammatory, anti-febrile, anti-allodynia (and anti-vulvodynia), anti-hyperalgesia, anti thermohypoalgesia, and anxiolytic propensities with a wider safety margins.