Industrial pharmacy

Antihistamines Overview. Notes on classic anti-H1 antihistamines. General formula, mepyramine, antazoline, diphenhydramine, promethazine. Phenothiazine Neuroleptics Etiological hypotheses on schizophrenia. Discovery of chlorpromazine. Chlorpromazine: synthesis and structure-activity relationships (SAR). Perazine and Phenazine. Trifluoperazine, thioridazine, mesoridazine, perphenazine, prochlorperazine, fluphenazine, trifluoperazine. Chlorprothixene (synthesis), thiothixene. Depot forms of phenothiazine and thioxanthene neuroleptics. Metabolism of phenothiazine neuroleptics. Atypical antipsychotics: clozapine (synthesis), clotiapine, loxapine, perlapine. Butyrophenone Neuroleptics Discovery of haloperidol. Haloperidol: synthesis and SAR. Trifluperidol, spiperone, droperidol, penfluridol, fluspirilene, pimozide. Benzamide Neuroleptics From local anesthetics to benzamide neuroleptics: benzocaine, procaine, procainamide, metoclopramide, sulpiride, amisulpride. Rauwolfia alkaloids: notes. Anxiolytics Discovery of benzodiazepines (chlordiazepoxide). The GABA_A receptor for GABA; the benzodiazepine receptor (BZR). BZR: full agonists (e.g., diazepam, flunitrazepam), inverse agonists (e.g., β–carbolines), antagonists (e.g., flumazenil). Therapeutic activities of benzodiazepines. Chlordiazepoxide, diazepam (synthesis), nordiazepam, bromazepam, nitrazepam, clonazepam, flunitrazepam, potassium clorazepate, lorazepam, oxazepam, alprazolam, triazolam (synthesis). SAR of benzodiazepines. Metabolism of benzodiazepines. Non-benzodiazepine BZR agonists (Z-drugs): zolpidem, zaleplon, zopiclone. Partial BZR agonists: imidazenil, bretazenil. Hypnotics-Sedatives Barbiturates: mechanism of action on GABA_A receptor, general formula, synthesis. Lipophilicity/hydrophilicity requirements and SAR. Amobarbital, aprobarbital, butabarbital, pentobarbital, secobarbital, thiopental, phenobarbital, mephobarbital, cyclobarbital, esobarbital. Sodium thiopental. Barbiturate metabolism. Melatonin agonists: ramelteon. Anticonvulsants Excitatory (glutamate) and inhibitory (GABA) amino acids: biosynthesis and catabolism. Ionotropic and metabotropic receptors. GABA-acting drugs: valproic acid, gabapentin, tiagabine, barbiturates, primidone, benzodiazepines, felbamate, topiramate. Glutamate-acting drugs: felbamate, topiramate, lamotrigine. T-type Ca²⁺ channel blockers: succinimides (ethosuximide, methosuximide, phensuximide), oxazolidinediones (trimethadione), valproic acid, zonisamide. K⁺ channel activators: retigabine. Na⁺ channel blockers: hydantoins (phenytoin, mephenytoin, ethotoin), iminostilbenes (carbamazepine, oxcarbazepine). Synthesis of phenytoin and phenobarbital. Antiparkinson Agents Biosynthesis and catabolism of dopamine and noradrenaline. Etiological hypotheses of PD. L-DOPA, carbidopa, benserazide. MAO inhibitors: selegiline, rasagiline. COMT inhibitors: tolcapone, entacapone. Amantadine, memantine. Bromocriptine, pergolide and dopamine agonists. Anticholinergics: trihexyphenidyl, procyclidine, biperiden. Serotonin Receptor Drugs 5-HT1A agonists: buspirone, gepirone; 5-HT1A antagonists: spiperone, 2-methoxyphenylpiperazine; 5-HT1B,D,F antagonists: sumatriptan, zolmitriptan, rizatriptan (triptans); 5-HT2 antagonists: spiperone, clozapine, trazodone, mirtazapine; 5-HT3 antagonists: cocaine, ondansetron, alosetron, granisetron (setrons); non-selective serotonergic agonists: ergot alkaloids. Antidepressants Monoamine hypothesis. NSRIs (non-selective): tricyclics: imipramine (synthesis), clomipramine, trimipramine, amitriptyline (synthesis), doxepin, dothiepin; non-tricyclics: venlafaxine, duloxetine. NARIs: tricyclic and tetracyclic: desipramine, nortriptyline, butriptyline, amoxapine, maprotiline, mianserin; non-tricyclics: nisoxetine, atomoxetine, reboxetine. SSRIs: zimelidine, nor-zimelidine, fluoxetine (synthesis), norfluoxetine, paroxetine, talopram, talsupram, citalopram, desmethylcitalopram, sertraline, desmethylsertraline, fluvoxamine. DNRIs: bupropion, mazindol, amitifadine. SARIs: trazodone. NaSSAs: mirtazapine. MAO inhibitors: iproniazid, phenelzine, tranylcypromine, moclobemide. Cholinergic hypothesis: mecamylamine. Melatonergic hypothesis: agomelatine. Glutamatergic hypothesis: ketamine (synthesis). Mood stabilizers: lithium salts. Analeptics Strychnine, pentylenetetrazol (synthesis), niketamide, pretcamide. Xanthine alkaloids (caffeine synthesis), theophylline salts, fenetylline, istradefylline. Opioid Analgesics Opium alkaloids: morphine, codeine, thebaine, papaverine. Endogenous opioids: enkephalins and endorphins. Mechanism of µ-opioid receptor agonists. Neurochemical basis of addiction: cocaine, amphetamines, µ- and κ-opioid agonists. Opioid receptors: µ, κ, δ, NOR. Morphine: structure, stereochemistry, SAR. Beckett and Casy model. Pharmacokinetics: morphine, 6-acetylmorphine, heroin, codeine. Hydromorphone and hydrocodone; oxymorphone, oxycodone. N17 substitution (agonists and antagonists): naloxone, naltrexone, nalorphine, nalbuphine, N-phenethylmorphine. Molecular simplification: morphinans: N-methylmorphinan, levorphanol, dextromethorphan, levallorphan, N-phenethyllevorphanol, butorphanol; benzomorphans: metazocine, phenazocine (synthesis), pentazocine, bremazocine; 4-phenylpiperidines and 4-anilinopiperidines: meperidine (synthesis), ketobemidone, fentanyl, sufentanil, alfentanil, remifentanil; 3-phenylpropylamines: methadone (synthesis), acetylmethadol, dextro- and levo-propoxyphene, loperamide, diphenoxylate. Molecular complication: oripavines: etorphine (synthesis), diprenorphine, buprenorphine. µ-opioid receptor models: Beckett & Casy (1954 & 1971), Portoghese (1965 & 1981), Snyder (1976). Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Salicylic acid, acetylsalicylic acid (synthesis). Arachidonic acid cascade. Diflunisal. Fenamates (mefenamic, meclofenamic acid). Arylacetic and α-arylpropionic acids: indomethacin (synthesis), sulindac, diclofenac (synthesis), ketoprofen (synthesis), ibuprofen, flurbiprofen, naproxen, etodolac, ketorolac. Pyrazolidinediones and pyrazolones: phenylbutazone, aminophenazone, dipyrone. Oxicams: piroxicam (synthesis), sudoxicam, isoxicam, meloxicam. Paracetamol, acetanilide, phenacetin. COX-2 selective inhibitors: nimesulide, celecoxib (synthesis), rofecoxib, valdecoxib, lumiracoxib. Cholinergic Nervous System Drugs Nicotinic and muscarinic receptors. Cholinergic agonists: acetylcholine, acetyl-α-methylcholine, methacholine, carbachol, bethanechol, pilocarpine. Indirect cholinomimetics: reversible acetylcholinesterase inhibitors: carbamoylating: physostigmine, neostigmine, pyridostigmine, rivastigmine; non-carbamoylating: tacrine, donepezil, galantamine. Irreversible AChE inhibitors: sarin, malathion, parathion, paraoxon. Antidotes: 2-PAM. Muscarinic antagonists: atropine, scopolamine, homatropine; pharmacophore development: adifenine, glycopyrrolate, trihexyphenidyl. Nicotinic antagonists: d-tubocurarine, decamethonium, succinylcholine, hexamethonium. Adrenergic Nervous System Drugs Noradrenaline and adrenaline: SAR, adrenergic receptors. β-selective agonists: isoprenaline, orciprenaline, isoetharine, tert-butyl-noradrenaline, terbutaline, salbutamol. Catecholamine structure simplification: synephrine, phenylephrine, metaraminol; ephedrine, norephedrine; amphetamine, methamphetamine. α-selective agonists: naphazoline (synthesis), clonidine (synthesis), α-methylDOPA. α-selective antagonists: prazosin (synthesis), terazosin, doxazosin; mirtazapine; dihydroergocristine, dihydroergotoxine. β-selective antagonists: dichloroisoprenaline, pronethalol, propranolol (synthesis). Arylethanolamines vs arylpropylamines. Oxprenolol, timolol, pindolol, nadolol. β1-selective blockers: acebutolol, atenolol, metoprolol, betaxolol. “Intelligent” β1-blockers: xamoterol. Non-selective α/β-blockers: labetalol, carvedilol. Cardiovascular Drugs Antiarrhythmics: quinidine, procainamide, lidocaine, phenytoin, propranolol, oxprenolol, nadolol, acebutolol. Calcium antagonists: verapamil, diltiazem, bepridil, 1,4-dihydropyridines (DHP). Nifedipine (synthesis and SAR), nitrendipine, nimodipine, isradipine. Coronary vasodilators: β-blockers, Ca²⁺ antagonists, organic nitrates (nitroglycerin, isosorbide dinitrate). Antihypertensives: adrenergics and antiadrenergics (prazosin, clonidine, α-methylDOPA, β-blockers); direct vasodilators (hydralazine, minoxidil, diazoxide); ACE inhibitors: captopril, enalapril and enalaprilat (SAR), lisinopril, fosinopril and fosinoprilat; sartans: losartan, eprosartan. Diuretics: osmotic (mannitol, sorbitol, isosorbide); carbonic anhydrase inhibitors (acetazolamide); loop (furosemide, ethacrynic acid); thiazide (chlorothiazide, hydrochlorothiazide, trichlormethiazide, hydroflumethiazide); potassium-sparing (spironolactone, canrenone, potassium canrenoate; triamterene, amiloride). Hypolipidemics: fibrates (clofibrate, fenofibrate, ciprofibrate), bile acid sequestrants (cholestyramine), statins (lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, rosuvastatin). HMG-CoA reductase inhibition mechanism. Steroids Stereochemistry. α-gonane and β-gonane. Steroid hormones, bile acids, and cardiotonic glycosides. Bile acids: chenodeoxycholic acid, ursodeoxycholic acid, obeticholic acid. Cardiotonic glycosides: lanatoside A, digitoxin, digoxin, ouabain. Notes on steroid hormone biosynthesis. Androgens: testosterone and its depot esters, androsterone, methyltestosterone. Progestins: progesterone, ethisterone. Estrogens: estrone, estradiol, ethinylestradiol, mestranol, quinestrol. Corticosteroids: mineralocorticoids (corticosterone, aldosterone), glucocorticoids (hydrocortisone, cortisone, prednisone, prednisolone, methylprednisolone, dexamethasone, betamethasone, triamcinolone). Steroid hormone mechanism of action. Steroid hormone receptors. Hours breakdown: CNS drugs: 45 hours Opioid and NSAID drugs: 15 hours ANS and cardiovascular drugs: 15 hours Steroids: 6 hours

**Essential:** To understand the lectures in *Pharmaceutical and Toxicological Chemistry 2*, knowledge of **organic chemistry**, **biochemistry**, **human anatomy**, and **physiology** is essential. **Important:** It is important to have acquired knowledge of **pathology**, **pharmacology**, **pharmacognosy**, and **toxicology**. **Useful:** It is useful to have prior knowledge of **general chemistry** and **drug analysis**.

Foye – Principi di Chimica Farmaceutica, Piccin Editore Patrick – Chimica Farmaceutica, EdiSES Editore Gasco, Gualtieri, Melchiorre – Chimica Farmaceutica, SEA Editore Artico – Lezioni di Chimica Farmaceutica, CISU Editore

not mandatory

Assessment Methods The course evaluation is based on an oral exam session scheduled each month of the year, excluding August. For each scheduled session, the instructor is also available to offer a deferred session (upon student request), held 15 days after the official date listed on Infostud. This is intended to provide students with the widest possible range of opportunities to take the exam—provided they are well-prepared. Indeed, students who do not pass the exam in the “standard” session will not be allowed to retake it during the deferred session, and their eligibility to attend the following session will be at the instructor’s discretion. The oral exam lasts approximately one hour per student, during which the instructor thoroughly examines the candidate’s knowledge across all parts of the syllabus. The goal of the exam is to assess the student’s knowledge of major drug classes, their identification, structure-activity relationships, molecular mechanisms, and biological effects. Topics must be discussed using language appropriate for a professional in pharmaceutical sciences. The evaluation is based on the following criteria: Knowledge of the subject across all therapeutic areas covered by the syllabus Use of appropriate scientific language Active participation during lectures Demonstrated reasoning skills during the oral exam Ability to study independently using the recommended textbooks A sufficient understanding of the topics in all areas of the syllabus is required to pass the exam with the minimum grade. To achieve the highest grade (30/30 with honors), the student must demonstrate excellent knowledge of all topics, the ability to connect concepts logically and coherently, and show that they have truly internalized and mastered the subject matter, navigating through it with confidence and fluency. In short, they must demonstrate something beyond mere memorization—a level of understanding that exceeds 100% of standard expectations.

The course Pharmaceutical and Toxicological Chemistry 2 consists of lectures delivered in person, occasionally complemented by one or two specific seminars. All lectures are interactive, with the instructor actively engaging students by asking questions that they are expected to answer based on knowledge acquired in previous courses. This approach helps highlight connections between the current course and prior coursework, whose foundational concepts are crucial for understanding the new material. These frequent references to earlier subjects aim to encourage students not to treat this course as an isolated topic, merely to be studied for the final exam and then forgotten. Instead, the goal is to promote a multidisciplinary study approach, which students must be trained for—especially by the fourth year, as they near the end of their academic journey. Slides and study materials (exam syllabus, recommended textbooks) will be made available on the e-learning platform to aid exam preparation. However, the slides are meant only as a guideline and cannot replace the recommended textbooks or the lectures themselves. Attendance is not mandatory but strongly recommended.