Zacopride: Difference between revisions

{{drugbox |

| IUPAC_name = 4-​amino-​''N''-​1-​azabicyclo[2.2.2]oct-​3-​yl-​5-​chloro-​2-​methoxybenzamide

| image = Zacopride.png

| width = 220

| CAS_number = 90182-92-6

| ATC_prefix = none

| ATC_suffix =

| PubChem = 108182

| DrugBank =

| C = 15 | H = 20 | Cl = 1 | N = 3 | O = 2

| molecular_weight = 309.791 g/mol

| smiles = COC1=CC(=C(C=C1C(=O)NC2CN3CCC2CC3)Cl)N

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life =

| excretion =

| pregnancy_category=

| legal_status =

| routes_of_administration =

'''Zacopride''' is a potent [[Antagonist (pharmacology)|antagonist]] at the [[5-HT3 receptor|5HT₃]] [[Receptor (biochemistry)|receptor]]<ref>{{cite journal | last1 = Smith | first1 = WW | last2 = Sancilio | first2 = LF | last3 = Owera-Atepo | first3 = JB | last4 = Naylor | first4 = RJ | last5 = Lambert | first5 = L | title = Zacopride, a potent 5-HT3 antagonist | journal = The Journal of pharmacy and pharmacology | volume = 40 | issue = 4 | pages = 301–2 | year = 1988 | pmid = 2900319 }}</ref> and an [[agonist]] at the [[5-HT4 receptor|5HT₄]] receptor.<ref>{{cite journal | last1 = Lefebvre | first1 = H | last2 = Contesse | first2 = V | last3 = Delarue | first3 = C | last4 = Soubrane | first4 = C | last5 = Legrand | first5 = A | last6 = Kuhn | first6 = JM | last7 = Wolf | first7 = LM | last8 = Vaudry | first8 = H | title = Effect of the serotonin-4 receptor agonist zacopride on aldosterone secretion from the human adrenal cortex: in vivo and in vitro studies | journal = The Journal of clinical endocrinology and metabolism | volume = 77 | issue = 6 | pages = 1662–6 | year = 1993 | pmid = 8263156 }}</ref> It has [[anxiolytic]]<ref>{{cite journal | last1 = Costall | first1 = B | last2 = Domeney | first2 = AM | last3 = Gerrard | first3 = PA | last4 = Kelly | first4 = ME | last5 = Naylor | first5 = RJ | title = Zacopride: anxiolytic profile in rodent and primate models of anxiety | journal = The Journal of pharmacy and pharmacology | volume = 40 | issue = 4 | pages = 302–5 | year = 1988 | pmid = 2900320 }}</ref> and [[nootropic]] effects in animal models,<ref>{{cite journal | last1 = Fontana | first1 = DJ | last2 = Daniels | first2 = SE | last3 = Eglen | first3 = RM | last4 = Wong | first4 = EH | title = Stereoselective effects of (R)- and (S)-zacopride on cognitive performance in a spatial navigation task in rats | journal = Neuropharmacology | volume = 35 | issue = 3 | pages = 321–7 | year = 1996 | pmid = 8783207 }}</ref> with the (R) enantiomer being the more active form.<ref>{{cite journal | last1 = Young | first1 = R | last2 = Johnson | first2 = DN | title = Anxiolytic-like activity of R(+)- and S(-)-zacopride in mice | journal = European journal of pharmacology | volume = 201 | issue = 2-3 | pages = 151–5 | year = 1991 | pmid = 1686755 }}</ref> It also has [[antiemetic]]<ref>{{cite journal | last1 = Yamakuni | first1 = H | last2 = Nakayama | first2 = H | last3 = Matsui | first3 = S | last4 = Imazumi | first4 = K | last5 = Matsuo | first5 = M | last6 = Mutoh | first6 = S | title = Inhibitory effect of zacopride on Cisplatin-induced delayed emesis in ferrets | journal = Journal of pharmacological sciences | volume = 101 | issue = 1 | pages = 99–102 | year = 2006 | pmid = 16651699 }}</ref> and pro-respiratory effects, both reducing [[sleep apnoea]]<ref>{{cite journal | last1 = Carley | first1 = DW | last2 = Depoortere | first2 = H | last3 = Radulovacki | first3 = M | title = R-zacopride, a 5-HT3 antagonist/5-HT4 agonist, reduces sleep apneas in rats | journal = Pharmacology, biochemistry, and behavior | volume = 69 | issue = 1-2 | pages = 283–9 | year = 2001 | pmid = 11420096 }}</ref> and reversing [[opioid]]-induced [[respiratory depression]] in animal studies.<ref>{{cite journal | last1 = Meyer | first1 = LC | last2 = Fuller | first2 = A | last3 = Mitchell | first3 = D | title = Zacopride and 8-OH-DPAT reverse opioid-induced respiratory depression and hypoxia but not catatonic immobilization in goats | journal = American journal of physiology. Regulatory, integrative and comparative physiology | volume = 290 | issue = 2 | pages = R405–13 | year = 2006 | pmid = 16166206 | doi = 10.1152/ajpregu.00440.2005 }}</ref>

Zacopride was found to significantly increase [[aldosterone]] levels in human subjects for 180 minutes at a dose of 400 micrograms. It is thought to do this by stimulating the 5-HT4 receptors on the adrenal glands. Zacropride also stimulated aldosterone secretion when applied to human adrenal glands <i>in vitro</i>. No significant changes were observed in [[renin]], [[ACTH]], or [[cortisol]] levels.<ref>{{cite journal | last1 = Lefebvre | first1 = H | last2 = Contesse | first2 = V | last3 = Delarue | first3 = C | last4 = Soubrane | first4 = C | last5 = Legrand | first5 = A | last6 = Kuhn | first6 = JM | last7 = Wolf | first7 = LM | last8 = Vaudry | first8 = H | title = Effect of the serotonin-4 receptor agonist zacopride on aldosterone secretion from the human adrenal cortex: in vivo and in vitro studies | journal = The Journal of clinical endocrinology and metabolism | volume = 77 | issue = 6 | pages = 1662–6 | year = 1993 | pmid = 8263156 }}</ref>

[[Category:Respiratory agents]]

[[Category:Serotonin receptor agonists]]

[[Category:Quinuclidines]]

[[Category:Aromatic amines]]

[[Category:Organochlorides]]