Norgestimate

Not to be confused with Norgestomet.

Norgestimate
Clinical data
Trade namesOrtho Tri-Cyclen, others
Other namesNGM; ORF-10131; Levonorgestrel acetate oxime; Levonorgestrel 17β-acetate 3-oxime; 17α-Ethynyl-18-methyl-19-nortestosterone 3-oxime 17β-acetate; 17α-Ethynyl-18-methylestr-4-en-17β-ol-3-one 3-oxime 17β-acetate
AHFS/Drugs.comProfessional Drug Facts
Professional Drug Facts
MedlinePlusa601050
License data
Pregnancy
category
  • Use is contraindicated
Routes of
administration		By mouth
Drug classProgestogen; Progestin; Progestogen ester[1]
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityUnknown[2]
Protein binding• Norelgestromin: 99% (to albumin)[1]
• Levonorgestrel: 98% (to albumin and SHBGTooltip sex hormone-binding globulin)[1]
• Levonorgestrel acetate: ? (to albumin)[1]
MetabolismLiver, intestines (deacetylation, reduction, hydroxylation, conjugation)[1][3][4]
Metabolites• Norelgestromin[1]
• Levonorgestrel[1]
• Levonorgestrel acetate[1]
Elimination half-life• Norgestimate: very short[1]
• Norelgestromin: 17–37 hours[3][1]
• Levonorgestrel: 24–32 hours[1]
ExcretionUrine: 47%[4]
Feces: 37%[4]
Identifiers
  • [(3E,8R,9S,10R,13S,14S,17R)-13-ethyl-17-ethynyl-3-hydroxyimino-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-yl] acetate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.167.085 Edit this at Wikidata
Chemical and physical data
FormulaC23H31NO3
Molar mass369.505 g·mol−1
3D model (JSmol)
Melting point214 to 218 °C (417 to 424 °F)
  • O=C(O[C@@]2(C#C)CC[C@H]1[C@H]4[C@H](CC[C@@]12CC)[C@@H]3/C(=C\C(=N\O)CC3)CC4)C
  • InChI=1S/C23H31NO3/c1-4-22-12-10-19-18-9-7-17(24-26)14-16(18)6-8-20(19)21(22)11-13-23(22,5-2)27-15(3)25/h2,14,18-21,26H,4,6-13H2,1,3H3/b24-17+/t18-,19+,20+,21-,22-,23-/m0/s1 checkY
  • Key:KIQQMECNKUGGKA-NMYWJIRASA-N checkY
  (verify)

Norgestimate, sold under the brand name Ortho Tri-Cyclen among others, is a progestin medication which is used in birth control pills for women and in menopausal hormone therapy.[1][3][4][5] The medication is available in combination with an estrogen and is not available alone.[6] It is taken by mouth.[1]

Side effects of the combination of an estrogen and norgestimate include menstrual irregularities, headaches, nausea, abdominal pain, breast tenderness, mood changes, and others.[3][4] Norgestimate is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone.[1] It has very weak androgenic activity and no other important hormonal activity.[1] The medication is a prodrug of norelgestromin and to a lesser extent of levonorgestrel in the body.[1]

Norgestimate was patented in 1965 and introduced for medical use, specifically in birth control pills, in 1986.[7][8] It was introduced for use in menopausal hormone therapy in the United States in 1999.[9] Norgestimate is sometimes referred to as a "third-generation" progestin.[10] It is marketed in birth control pills widely throughout the world, whereas it is available for use in menopausal hormone therapy only in the United States and Brazil.[6] Norgestimate is available as a generic medication.[11] In 2022, the combination with ethinylestradiol was the 99th most commonly prescribed medication in the United States, with more than 6 million prescriptions.[12][13]

Medical uses

Norgestimate is used in hormonal contraception and in menopausal hormone therapy for the treatment of menopausal symptoms.[5] It is used in combination with ethinylestradiol in birth control pills and in combination with estradiol in menopausal hormone therapy.[6][14]

Available forms

Norgestimate is available only in combination with the estrogens ethinylestradiol and estradiol.[6] These formulations are for use by mouth and are indicated specifically for hormonal contraception and menopausal hormone therapy.[6] Norgestimate is not available on its own (i.e., as a standalone medication).[6]

Contraindications

See also: Progestin § Contraindications

Side effects

See also: Norelgestromin § Side effects, and Progestin § Side effects

Norgestimate has mostly been studied in combination with an estrogen, so the side effects of norgestimate specifically or on its own have not been well-defined.[3][4]

Side effects associated with the combination of ethinylestradiol and norgestimate in premenopausal women, with greater than or equal to 2% incidence over up to 24 menstrual cycles, include headache/migraine (33%), abdominal/gastrointestinal pain (7.8%), vaginal infection (8.4%), vaginal discharge (6.8%), breast issues (including breast pain, discharge, and enlargement) (6.3%), mood disorders (including depression and mood alterations) (5.0%), flatulence (3.2%), nervousness (2.9%), and rash (2.6%).[4]

Side effects associated with the combination of estradiol and norgestimate in postmenopausal women, with greater than or equal to 5% incidence over one year, include headache (23%), upper respiratory tract infection (21%), breast pain (16%), back pain (12%), abdominal pain (12%), flu-like symptoms (11%), arthralgia (9%), vaginal bleeding (9%), dysmenorrhea (8%), sinusitis (8%), vaginitis (7%), pharyngitis (7%), fatigue (6%), pain (6%), nausea (6%), viral infection (6%), flatulence (5%), tooth disorder (5%), myalgia (5%), dizziness (5%), depression (5%), and coughing (5%).[3]

Overdose

See also: Progestin § Overdose

Interactions

See also: Progestin § Interactions

Pharmacology

Pharmacodynamics

Norelgestromin, also known as 17β-deacetylnorgestimate, the main active metabolite of norgestimate.

Norgestimate is a rapidly and completely converted prodrug, mainly of norelgestromin (17β-deacetylnorgestimate or levonorgestrel 3-oxime), but also of levonorgestrel (3-keto-17β-deacetylnorgestimate) to a lesser extent (22 ± 6% of an administered dose or about 40–70 μg)[2] and of levonorgestrel acetate (levonorgestrel 17β-acetate) in very small amounts.[1][5][15][16][17] Via its active metabolites, norgestimate has progestogenic activity, antigonadotropic effects, very weak androgenic activity, and no other important hormonal activity.[1]

Relative affinities (%) of norgestimate and metabolites
Compound PRTooltip Progesterone receptor ARTooltip Androgen receptor ERTooltip Estrogen receptor GRTooltip Glucocorticoid receptor MRTooltip Mineralocorticoid receptor SHBGTooltip Sex hormone-binding globulin CBGTooltip Corticosteroid binding globulin
Norgestimate 15 0 0 1 0 0 0
Norelgestromin (17β-deAc-NGM) 10 0 ? ? ? 0 ?
Levonorgestrel (3-keto-17β-deAc-NGM) 150–162 45 0 1–8 17–75 50 0
Levonorgestrel 17β-acetate (3-keto-NGM) 135 ? 0 ? ? 0 ?
Notes: Values are percentages (%). Reference ligands (100%) were promegestone for the PRTooltip progesterone receptor, metribolone for the ARTooltip androgen receptor, E2 for the ERTooltip estrogen receptor, DEXATooltip dexamethasone for the GRTooltip glucocorticoid receptor, aldosterone for the MRTooltip mineralocorticoid receptor, DHTTooltip dihydrotestosterone for SHBGTooltip sex hormone-binding globulin, and cortisol for CBGTooltip Corticosteroid-binding globulin. Sources: [18][1][19]

Progestogenic activity

Norgestimate is a progestogen, or an agonist of the progesterone receptor.[1] The relative binding affinities of norgestimate and its active metabolites for the progesterone receptor compared to promegestone (100%) are 15% for norgestimate, 10% for norelgestromin, 150% for levonorgestrel, and 135% for levonorgestrel acetate.[1] Because of their low concentrations, norgestimate and levonorgestrel acetate are not thought to contribute significantly to the biological activity of norgestimate.[1] In addition, although levonorgestrel binds to the progesterone receptor with much higher affinity than norelgestromin, levonorgestrel has high affinity for sex hormone-binding globulin (SHBG) (87% of that of testosterone), which may limit its activity, whereas norelgestromin does not bind to SHBG.[1][4][20] The ovulation-inhibiting dosage of norgestimate is 200 μg/day.[1]

Androgenic activity

In addition to its progestogenic activity, norgestimate has weak androgenic activity.[1] However, the medication shows less androgenic activity than related 19-nortestosterone progestins like levonorgestrel and norethisterone.[5][21] Norgestimate and norelgestromin have negligible affinity for the androgen receptor (both 0% of the affinity of metribolone), while levonorgestrel has considerable affinity for the androgen receptor (45% of that of metribolone).[1] In addition to their lack of affinity for the androgen receptor, norgestimate and norelgestromin have virtually no affinity for SHBG, and therefore do not displace testosterone from this carrier protein (although levonorgestrel does still bind with high affinity to SHBG and hence could increase free testosterone levels via occupation of SHBG).[5][1] In accordance, clinical trials of norgestimate have observed minimal androgenic side effects in women treated with the medication.[21] As an example, clinical studies have found that norgestimate does not appreciably inhibit the increase in SHBG levels produced by ethinylestradiol.[20] This is of interest because estrogens increase and androgens decrease liver production of SHBG and by extension circulating levels of SHBG.[20]

The relative binding affinity of norgestimate and its metabolite norelgestromin for the rat prostatic androgen receptor (AR) are 0.3% and 1.3% of those of dihydrotestosterone (DHT), respectively, whereas the respective values for levonorgestrel and gestodene are 22% and 15%.[20] Based on these findings, the ratios of AR to PR binding are 219 for norgestimate and 48 for norelgestromin, whereas the ratios for progesterone, levonorgestrel, and gestodene are 93, 11, and 28, respectively.[20] As such, norgestimate and norelgestromin would appear to have much lower androgenic potency than other 19-nortestosterone progestins.[20] However, levonorgestrel is an important metabolite of both norgestimate and norelgestromin, and it may serve to increase their androgenic potency to some degree.[1][20]

When norgestimate is combined with ethinylestradiol, which is potently antiandrogenic, there are only antiandrogenic effects overall and the combination is suitable for treatment of hyperandrogenism.[14]

Other activities

Norgestimate and its active metabolites do not bind to other steroid hormone receptors besides the progesterone and androgen receptors and hence have no other off-target hormonal activity.[1] This includes estrogenic, glucocorticoid, antimineralocorticoid, and neurosteroid activity.[1] However, levonorgestrel has been found to inhibit 5α-reductase and hepatic cytochrome P450 enzymes in vitro to some extent.[1]

Pharmacokinetics

Norgestimate is rapidly and almost completely metabolized into its active metabolites, mainly norelgestromin (the primary active metabolite) and to a lesser extent levonorgestrel, upon oral ingestion.[1][3][4] As a result, only very low concentrations (70 pg/mL) of norgestimate itself are detectable in the circulation, and only for about 6 hours after an oral dose.[1][22] The oral bioavailability of norgestimate is unknown.[22][2] This is due to the rapid and extensive metabolism of norgestimate, which makes determination of overall bioavailability difficult and necessitates methods other than area-under-the-curve (AUC) to do so.[22] Peak levels of norelgestromin (3,500 pg/mL) are reached at approximately 2 hours following administration of norgestimate.[3][4][14] Co-administration of norgestimate with a high-fat meal has been found to significantly decrease peak levels of norelgestromin, although the area-under-the-curve levels of norelgestromin are not significantly altered by food.[3] Steady-state levels of norelgestromin and levonorgestrel are reached within 21 days of treatment with norgestimate.[4] There is an approximate 2-fold accumulation in levels of norelgestromin and a non-linear approximate 8-fold accumulation in levels of levonorgestrel with continuous administration of norgestimate.[4] The accumulation of levonorgestrel is thought to be a result of its high affinity for SHBG, which limits its biological activity.[4] The plasma protein binding of norelgestromin is approximately 99% and it is bound to albumin but not to SHBG.[3][4][1] Conversely, levonorgestrel is approximately 98% bound to plasma proteins and is bound to both albumin and SHBG.[1][4]

Norgestimate is extensively metabolized into its active metabolites during first-pass metabolism in the liver and intestines.[1][3][4] The major metabolite of norgestimate is norelgestromin and is formed from norgestimate via deacetylation in the liver and intestines.[3] A more minor metabolite of norgestimate is levonorgestrel, which accounts for 20 to 25% (22 ± 6%) of an administered dose or about 40 to 70 μg norgestimate,[22][2] and a very minor metabolite of norgestimate is levonorgestrel 17β-acetate.[3] Both of these metabolites are active similarly to norgelstromin.[1][3] With a typical oral contraceptive dosage of norgestimate of 200 to 250 μg/day, an amount of 50 to 60 μg/day levonorgestrel may be produced.[22] This is similar to the ovulation-inhibiting dosage of levonorgestrel, and suggests that norgestimate may act in considerable part as a prodrug specifically of levonorgestrel.[22][1] Following their formation, the active metabolites of norgestimate are inactivated via reduction, hydroxylation, and conjugation into levonorgestrel metabolites.[1][4] The terminal half-life of norelgestromin is between 17 and 37 hours and of levonorgestrel is between 24 and 32 hours.[3][1] The metabolites of norgestimate are eliminated 47% in urine and 37% in feces.[3][4] Unchanged norgestimate is undetectable in urine.[4]

Chemistry

See also: List of progestogens, Progestogen ester, and List of progestogen esters

Norgestimate, also known as 17α-ethynyl-18-methyl-19-nortestosterone 3-oxime 17β-acetate or as 17α-ethynyl-18-methylestr-4-en-17β-ol-3-one 3-oxime 17β-acetate, is a synthetic estrane steroid and a derivative of testosterone.[23][6] It is a racemic mixture of E and Z isomers.[24] Norgestimate is more specifically a derivative of norethisterone (17α-ethynyl-19-nortestosterone) and is a member of the gonane (18-methylestrane) subgroup of the 19-nortestosterone family of progestins.[25] It is the C3 oxime and C17β acetate ester of levonorgestrel and is also known as levonorgestrel acetate oxime.[26] A related compound is norethisterone acetate oxime (norethisterone-3-oxime 17β-acetate).[23]

History

Norgestimate was introduced as a component of combined oral contraceptives in 1986.[7] Based on its year of introduction, norgestimate is sometimes described as a "third-generation" progestin.[10] Norgestimate was approved in combination with estradiol for use in menopausal hormone therapy in 1999 in the United States, and a generic version of this preparation became available in this country in 2005.[9]

Society and culture

Generic names

Norgestimate is the generic name of the drug and its INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, USPTooltip United States Pharmacopeia, BANTooltip British Approved Name, and DCFTooltip Dénomination Commune Française.[23][6] It is also known by its developmental code name ORF-10131.[23][6]

Brand names

Norgestimate is marketed in combination with ethinylestradiol as a birth control pill under the brand names Amicette, Cilest, Cyclen, Edelsin, Effiprev, Estarylla, MonoNessa, Orlon, Ortho Tri-Cyclen, Ortho Tri-Cyclen Lo, Ortho-Cyclen, Pramino, Previfem, Sprintec, Triafemi, TriCilest, Tri-Cyclen, Tri-Cyclen LO, Tridette, Tri-Estarylla, Tri-Linyah, TriNessa, Tri-Previfem, and Tri-Sprintec.[23][6] It is marketed in combination with estradiol for menopausal hormone therapy under the brand name Prefest.[6]

Availability

Norgestimate in combination with ethinylestradiol is marketed widely throughout the world, including in the United States, Canada, the United Kingdom, Ireland, elsewhere throughout Europe, South Africa, Latin America, and Asia.[6] Unlike the combined birth control pills of norgestimate with ethinylestradiol, the combination of norgestimate with estradiol, sold under the brand name Prefest for menopausal hormone therapy, is reportedly only marketed in the United States and Brazil.[6]

Research

A 2017 study found that norgestimate inhibits staphylococcal biofilm formation and resensitizes methicillin-resistant Staphylococcus aureus to β-lactam antibiotics.[27] In contrast, norelgestromin showed much weaker activity, indicating that the acetyl group of norgestimate is important for the activity.[27] It was suggested by the researchers that norgestimate may be a promising lead compound for the development of new antibiotics.[27]

References

  1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an Kuhl H (August 2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration". Climacteric. 8 (Suppl 1): 3–63. doi:10.1080/13697130500148875. PMID 16112947. S2CID 24616324.
  2. ^ a b c d Fotherby K (August 1996). "Bioavailability of orally administered sex steroids used in oral contraception and hormone replacement therapy". Contraception. 54 (2): 59–69. doi:10.1016/0010-7824(96)00136-9. PMID 8842581.
  3. ^ a b c d e f g h i j k l m n o p "Prefest- estradiol/norgestimate kit". DailyMed. 29 February 2016. Retrieved 9 November 2020.
  4. ^ a b c d e f g h i j k l m n o p q r s "Ortho Tri Cyclen- norgestimate and ethinyl estradiol kit Ortho Cyclen- norgestimate and ethinyl estradiol kit". DailyMed. 16 May 2019. Retrieved 9 November 2020.
  5. ^ a b c d e Lemke TL, Williams DA (2008). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 1316–. ISBN 978-0-7817-6879-5.
  6. ^ a b c d e f g h i j k l m "Norgestimate and Ethinyl Estradiol - FDA prescribing information, side effects and uses".
  7. ^ a b van Keep PA, Rekers H (6 December 2012). "Trends in Contraception and Contraceptive Research". In Runnebaum BC, Rabe T, Kiesel L (eds.). Female Contraception: Update and Trends. Springer Science & Business Media. pp. 13–. ISBN 978-3-642-73790-9.
  8. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 479. ISBN 9783527607495.
  9. ^ a b Food and Drug Administration (15 August 2023). Approved Drug Products with Therapeutic Equivalence Evaluations - FDA Orange Book 33rd Edition (2013): FDA Orange Book 33rd Edition (2013). Logos Press. pp. 190–. ISBN 978-1-934899-83-0.
  10. ^ a b Carp HJ (9 April 2015). Progestogens in Obstetrics and Gynecology. Springer. p. 112. ISBN 978-3-319-14385-9.
  11. ^ "Generic Ortho Tri-Cyclen Availability". Drugs.com.
  12. ^ "The Top 300 of 2022". ClinCalc. Archived from the original on 30 August 2024. Retrieved 30 August 2024.
  13. ^ "Ethinyl Estradiol; Norgestimate Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Retrieved 30 August 2024.
  14. ^ a b c Henzl MR (July 2001). "Norgestimate. From the laboratory to three clinical indications". The Journal of Reproductive Medicine. 46 (7): 647–661. PMID 11499185.
  15. ^ Falcone T, Hurd WW (2007). Clinical Reproductive Medicine and Surgery. Elsevier Health Sciences. pp. 389–. ISBN 978-0-323-03309-1.
  16. ^ IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, World Health Organization, International Agency for Research on Cancer (2007). Combined Estrogen-progestogen Contraceptives and Combined Estrogen-progestogen Menopausal Therapy. World Health Organization. pp. 150–151. ISBN 978-92-832-1291-1.
  17. ^ Stanczyk FZ (September 2002). "Pharmacokinetics and potency of progestins used for hormone replacement therapy and contraception". Reviews in Endocrine & Metabolic Disorders. 3 (3): 211–224. doi:10.1023/A:1020072325818. PMID 12215716. S2CID 27018468.
  18. ^ Kuhl H (September 1990). "Pharmacokinetics of oestrogens and progestogens". Maturitas. 12 (3): 171–197. doi:10.1016/0378-5122(90)90003-o. PMID 2170822.
  19. ^ Philibert D, Bouchoux F, Degryse M, Lecaque D, Petit F, Gaillard M (October 1999). "The pharmacological profile of a novel norpregnance progestin (trimegestone)". Gynecological Endocrinology. 13 (5): 316–326. doi:10.3109/09513599909167574. PMID 10599548.
  20. ^ a b c d e f g Phillips A, Hahn DW, McGuire JL (October 1992). "Preclinical evaluation of norgestimate, a progestin with minimal androgenic activity". American Journal of Obstetrics and Gynecology. 167 (4 Pt 2): 1191–1196. doi:10.1016/s0002-9378(12)90410-x. PMID 1415445.
  21. ^ a b Chapdelaine A, Desmarais JL, Derman RJ (1989). "Clinical evidence of the minimal androgenic activity of norgestimate". International Journal of Fertility. 34 (5): 347–352. PMID 2571595.
  22. ^ a b c d e f Mishell DR (10 November 1999). Progestins and Antiprogestins in Clinical Practice. Taylor & Francis. pp. 133–151. ISBN 978-0-8247-8291-7.
  23. ^ a b c d e Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 887–. ISBN 978-1-4757-2085-3.
  24. ^ US 7345183, Tombari DG, Vecchioli A, "Process for obtaining norelgestromin in different relations of isomers e and Z", issued 18 March 2008, assigned to Gador SA 
  25. ^ Schreiber CA, Barnhart K (2009). "Chapter 36 - Contraception". In Strauss JF, Barbieri RL (eds.). Yen and Jaffe's Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management. Elsevier Health Sciences. pp. 878–. ISBN 978-1-4160-4907-4.
  26. ^ Skouby SO (15 July 1997). Clinical Perspectives on a New Gestodene Oral Contraceptive Containing 20 μg of Ethinylestradiol. CRC Press. pp. 11–. ISBN 978-1-85070-786-8.
  27. ^ a b c Yoshii Y, Okuda KI, Yamada S, Nagakura M, Sugimoto S, Nagano T, et al. (2017). "Norgestimate inhibits staphylococcal biofilm formation and resensitizes methicillin-resistant Staphylococcus aureus to β-lactam antibiotics". npj Biofilms and Microbiomes. 3: 18. doi:10.1038/s41522-017-0026-1. PMC 5522392. PMID 28758016.{{cite journal}}: CS1 maint: overridden setting (link)

Further reading

  • Henzl MR (July 2001). "Norgestimate. From the laboratory to three clinical indications". The Journal of Reproductive Medicine. 46 (7): 647–661. PMID 11499185.
  • Curran MP, Wagstaff AJ (2001). "Estradiol and norgestimate: a review of their combined use as hormone replacement therapy in postmenopausal women". Drugs & Aging. 18 (11): 863–885. doi:10.2165/00002512-200118110-00007. PMID 11772126. S2CID 22720686.
  • Curran MP, Wagstaff AJ (2002). "Spotlight on estradiol and norgestimate as hormone replacement therapy in postmenopausal women". Treatments in Endocrinology. 1 (2): 127–129. doi:10.2165/00024677-200201020-00006. PMID 15765628. S2CID 1936039.

Read other articles:

Jiwaku

JiwakuAlbum studio karya Ruth SahanayaDirilis8 Mei 2006Direkam2005 - 2006GenrePopLabelSony BMG Music EntertainmentKronologi Ruth Sahanaya Bicara Cinta (2003)Bicara Cinta2003 Jiwaku (2006) Thankful (2010)Thankful2010 Jiwaku merupakan sebuah album musik ketujuh karya Ruth Sahanaya. Album ini dirilis pada tahun 2006 dan berisi 9 buah lagu dengan hits singel lagu Jiwaku. Daftar lagu Jiwaku Layu Sebelum Berkembang Rubahlah Hatiku Camar Yang Pulang Semua Jadi Satu - featuring Kris Dayanti &...

 

Aftercastle

Structure behind mizzenmast on sailing ships This article relies largely or entirely on a single source. Relevant discussion may be found on the talk page. Please help improve this article by introducing citations to additional sources.Find sources: Aftercastle – news · newspapers · books · scholar · JSTOR (November 2018) Aftercastle of the frigate Méduse, as seen from the deck Galleon showing both a forecastle (left) and aftercastle (right) Stern of ...

 

Brunswick, New York

Town in New York, United StatesBrunswickTownSkyline of Brunswick from Pinewoods Avenue FlagSealMap of Brunswick and its major thoroughfaresLocation in Rensselaer County and the state of New York.BrunswickLocation within New YorkCoordinates: 42°44′57″N 73°35′23″W / 42.74917°N 73.58972°W / 42.74917; -73.58972Country United StatesState New YorkCountyRensselaerSettled1715Incorporated1807Government • SupervisorPhilip H. Herrington (Republican) ...

I'd Die Without You

1992 single by P.M. Dawn I'd Die Without YouSingle by P.M. Dawnfrom the album Boomerang: Original Soundtrack Album B-sideOn a Clear DayReleasedSeptember 4, 1992 (1992-09-04)[1]GenreR&BLength 4:11 (album version) 3:48 (radio edit) Label Gee Street LaFace Songwriter(s)Attrell CordesProducer(s)P.M. DawnP.M. Dawn singles chronology Paper Doll (1992) I'd Die Without You (1992) Looking Through Patient Eyes (1993) I'd Die Without You is a song by American R&B duo P.M. ...

 

Red Scare (podcast)

American culture and comedy podcast PodcastRed ScarePresentationHosted byAnna KhachiyanDasha NekrasovaGenreCultural criticismhumorpoliticsLanguageEnglishLength60–120 minutesCountry of originUnited StatesProductionProductionMeg Murnane (Mar–Oct 2018), subsequently self-producedTheme music composed byTrevor HornMartin KierszenbaumOpening themeAll the Things She Said by t.A.T.uAudio formatMP3No. of episodes375PublicationOriginal releaseMarch 29, 2018; 6 years ago (2018-03-2...

 

コルク

この記事は検証可能な参考文献や出典が全く示されていないか、不十分です。出典を追加して記事の信頼性向上にご協力ください。（このテンプレートの使い方）出典検索?: コルク – ニュース · 書籍 · スカラー · CiNii · J-STAGE · NDL · dlib.jp · ジャパンサーチ · TWL（2017年4月） コルクを打ち抜いて作った瓶の栓 コルク（木栓、�...

Mitsui Golden Glove Award

The Mitsui Golden Glove Award, sponsored by Japan's Mitsui Group, is an annual award for the best fielders in Japan's professional baseball leagues by the Nippon Professional Baseball Association. It is awarded to nine fielders. The players are selected based on votes by TV, radio, and newspaper journalists with over 5 years experience covering Japanese professional baseball. The trophy is accompanied by prize money.[1] See also Nippon Professional Baseball § Awards Baseball awa...

 

Kantianism

Philosophy of Immanuel Kant, a German philosopher This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages) This article's factual accuracy is disputed. Relevant discussion may be found on the talk page. Please help to ensure that disputed statements are reliably sourced. (March 2008) (Learn how and when to remove this message) This article includes a list of general references, but it lacks suffic...

 

Rope start

Manual engine starter Starting a Lazair II ultralight aircraft's JPX PUL 425 engine, equipped with a recoil starter. Rope start (also called pull start[citation needed] or rewind start[citation needed]) is a method of starting an internal combustion engine, usually on small machines, such as lawn mowers, chainsaws, grass trimmers, ultralight aircraft, small outboard motors and portable engine-generators. Also used on some small vehicles such as small go-karts, minibikes, and s...

Avilés

City and municipality in Asturias, Spain For other uses, see Avilés (disambiguation). Municipality in Asturias, SpainAvilésMunicipalitySan Francisco street FlagCoat of armsLocation of AvilésAvilésCoordinates: 43°33′22″N 5°54′30″W / 43.55611°N 5.90833°W / 43.55611; -5.90833CountrySpainAutonomous communityAsturiasComarcaAvilésCapitalAvilésGovernment • MayorMariví Monteserín (PSOE)Area • Total26.81 km2 (10.35 sq m...

 

Carroll Hubbard

American politician (1937–2022) Carroll HubbardOfficial portrait, 1991Member of the U.S. House of Representativesfrom Kentucky's 1st districtIn officeJanuary 3, 1975 – January 3, 1993Preceded byFrank StubblefieldSucceeded byThomas BarlowMember of the Kentucky SenateIn office1968–1975 Personal detailsBorn(1937-07-07)July 7, 1937Murray, Kentucky, U.S.DiedNovember 12, 2022(2022-11-12) (aged 85)Paducah, Kentucky, U.S.Political partyDemocratic (before 2019)Republica...

 

2018–19 Port Vale F.C. season

Port Vale 2018–19 football seasonPort Vale2018–19 seasonChairmanNorman SmurthwaiteManagerNeil Aspin(until 30 January)[1]Danny Pugh(caretaker 30 January – 4 February)John Askey(from 4 February)[2]StadiumVale ParkEFL League Two20th (49 points)FA CupFirst round(knocked out by Sunderland)EFL CupFirst round(knocked out by Lincoln City)EFL TrophyQuarter-finals(knocked out by Bristol Rovers)Player of the YearScott BrownTop goalscorerLeague: Tom Pope (11)All: Tom Pope (14)Highe...

After Thomas

After ThomasSampul DVDPembuatBBC AmericaHartswood FilmsPemeranKeeley HawesBen MilesAndrew ByrneSheila HancockDuncan PrestonNegara asal Britania RayaProduksiLokasi produksi Broadstairs, Kent, Inggris, Britania RayaDurasi93 menitRilis asliJaringanITVRilis26 December 2006 After Thomas adalah drama televisi yang disiarkan di Britania Raya oleh ITV. Acara ini dibintangi oleh Keeley Hawes, Ben Miles, Andrew Byrne, Sheila Hancock dan Duncan Preston. Sinopsis Nicola (Keeley Hawes) dan Rob Graham (Be...

 

Li Haiqiang

Chinese-born Hong Kong footballer Li Haiqiang Personal informationFull name Li HaiqiangDate of birth (1977-05-03) 3 May 1977 (age 47)Place of birth Meixian, Guangdong, ChinaHeight 1.81 m (5 ft 11 in)Position(s) MidfielderYouth career Guangdong HongyuanSenior career*Years Team Apps (Gls)1997–2002 Guangdong Hongyuan 2002–2003 Qingdao Hailifeng 34 (6)2003–2004 Dongguan Dongcheng 25 (4)2004–2006 Chengdu Wuniu 4 (0)2006–2012 South China 84 (12)2012–2013 Tuen Mun 14 ...

 

Glove (film)

GlovePoster filmNama lainHangul글러브 Alih Aksara yang DisempurnakanGeulreobeuMcCune–ReischauerKŭlrŏbŭ SutradaraKang Woo-sukProduserKatharine KimJung Sun-youngDitulis olehKim Kee-bumPemeranJung Jae-youngYoo SunPenata musikJo Yeong-wookSinematograferKim Yong-heungLee Bong-jooPenyuntingKo Im-pyoDistributorCJ EntertainmentTanggal rilis 20 Januari 2011 (2011-01-20) Durasi144 menitNegaraKorea SelatanBahasaKoreaPendapatankotorUS$12,188,145[1] Glove (Hangul: ...

Tuning fork

Device that generates sounds of constant pitch when struck Tuning fork by John Walker stamped with note (E) and frequency in hertz (659) A tuning fork is an acoustic resonator in the form of a two-pronged fork with the prongs (tines) formed from a U-shaped bar of elastic metal (usually steel). It resonates at a specific constant pitch when set vibrating by striking it against a surface or with an object, and emits a pure musical tone once the high overtones fade out. A tuning fork's pitch dep...

 

Malcolm Grant

British lawyer, chairman of NHS England For other people named Malcolm Grant, see Malcolm Grant (disambiguation). SirMalcolm GrantCBE FAcSSChairman of NHS EnglandIn office19 October 2011 – 30 October 2018Preceded byOffice establishedSucceeded byThe Lord Prior of BramptonChancellor of the University of YorkIn office27 October 2015 – Summer 2022Preceded byGreg DykeSucceeded byHeather MelvillePresident and Provost of University College LondonIn office1 August 2003 –&...

 

سيفيل (أوهايو)

سيفيل     الإحداثيات 41°00′56″N 81°51′52″W / 41.0156°N 81.8644°W / 41.0156; -81.8644   [1] سبب التسمية إشبيلية  تقسيم إداري  البلد الولايات المتحدة[2][3]  التقسيم الأعلى مقاطعة مدينا  خصائص جغرافية  المساحة 6.741683 كيلومتر مربع6.740477 كيلومتر مربع (1 أبريل 2010)...

Musei Vaticani

Musei Vaticani Ingresso al museo su viale Vaticano, in territorio italiano UbicazioneStato Città del Vaticano LocalitàCittà del Vaticano IndirizzoViale Vaticano 6, I-00192, Roma Coordinate41°54′23″N 12°27′16″E41°54′23″N, 12°27′16″E CaratteristicheTipoarcheologia, pittura, scultura, filatelia e numismatica Istituzione1506 FondatoriPapa Giulio II Apertura1771 DirettoreBarbara Jatta Visitatori6,764,858 (2023)[1] Sito web Modifica dati su Wikidata · Manua...

 

Victoria Falls Airport

Airport in Victoria Falls, ZimbabweVictoria Falls AirportIATA: VFAICAO: FVFASummaryAirport typeCivilOperatorCivil Aviation Authority of ZimbabweServesVictoria FallsLocationVictoria Falls, ZimbabweElevation AMSL3,490 ft / 1,064 mCoordinates18°05′45″S 25°50′20″E / 18.09583°S 25.83889°E / -18.09583; 25.83889MapVFALocation in ZimbabweRunways Direction Length Surface m ft 12/30 4,000 13,123 Asphalt Sources: GCM,[1] WAD,[2] Victori...