KH-3
Common Name(s): 2-diethylaminoethyl 4-aminobenzoate hydrochloride, GeroVita, Gerovital H3, GH-3, KH-3, Procaine hydrochloride
Medically reviewed by Drugs.com. Last updated on Dec 22, 2023.
Clinical Overview
Use
Clinical trial data are lacking to support use of KH-3 or other procaine preparations for depression or age-related diseases (eg, cognitive impairment, dementia). Adverse effects may limit therapeutic applications. Gerovital (KH-3) and similar products require an approved Abbreviated New Drug Application (ANDA) for legal marketing in the United States.
Dosing
There is no clinical evidence to support specific dosage recommendations for KH-3 or other procaine preparations.
Contraindications
Coadministration with anticholinesterase and anticholinergic agents is a potential contraindication. KH-3 is contraindicated in patients with known hypersensitivity to the drug.
Pregnancy/Lactation
Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.
Interactions
None well documented. Theoretical interactions exist. Coadministration with anticholinesterase and anticholinergic agents is a potential contraindication.
Adverse Reactions
Reports describe heartburn, restlessness, dizziness, migraine, and SLE following treatment with KH-3.
Toxicology
No data.
Source
KH-3 is typically included as an ingredient in nutritional supplement products; preparations vary regarding procaine hydrochloride content. Procaine preparations are said to be available in more than 70 countries and used by more than 100 million individuals.(Szatmari 2008)
History
KH-3 was developed in Germany in the 1960s and was popularized by Romanian and other Eastern European researchers.(Kent 1976) Gerovital (KH-3) and similar products require an approved ANDA for legal marketing in the United States.(Perls 2013)
These products have been administered parenterally and orally for their effects on the overall aging process and for the treatment of cerebral atherosclerosis, progressive dementia, arthritis, hair loss, hypertension, and sexual dysfunction.(Perls 2013)
Related/similar drugs
turmeric, Ginkgo Biloba
Chemistry
Pharmacologic effects are primarily due to procaine hydrochloride content, with preparations marketed as mixtures of procaine, buffers (eg, benzoic acid, potassium metabisulfate), analgesics, and nutritional supplements.(Brodaty 1990) One preparation from Germany contains procaine, hematoporphyrin (to aid absorption of procaine), magnesium carbonate, sodium hydrogen phosphate, potassium hydrochloride, and other compounds. Most products contain approximately 2% procaine hydrochloride. Studies have shown that biotrophic treatment with Gerovital H3 has a strong influence on glucose-6-phosphate dehydrogenase, with a tendency to diminish the thermolabile fractions.(MacFarlane 1975)
Uses and Pharmacology
Procaine has been used for decades as a local anesthetic and antiarrhythmic. The compound has several pharmacologic characteristics, including an ability to decrease membrane excitability and alter membrane ionic transmission. Procaine is hydrolyzed rapidly to inactive compounds by plasma enzymes.(Brodaty 1990)
Cholesterol
Reports of the effect of procaine on blood cholesterol levels are inconsistent, with some studies showing a reduction in cholesterol and others showing little beneficial effect.(Jarvik 1975)
CNS effects
Age-related cognitive impairment/dementia
Numerous studies have been conducted to evaluate the efficacy of procaine hydrochloride or commercially available mixtures of this compound for the treatment of a variety of organic diseases in aging individuals.(Orgogozo 1987)
Clinical data
A Cochrane review evaluating effects of procaine on cognitive decline and dementia identified 3 clinical trials meeting inclusion criteria; the population studied included those with dementia as well as healthy elderly participants. Pooled data from 2 studies (n=415) showed procaine had a detrimental effect in terms of adverse effects (20 of 208 patients with active treatment vs 3 of 207 with placebo; odds ratio, 7.3 [95% CI, 2.13 to 25]; P=0.002); a single small study of 12 women with dementia also suggested a detrimental effect. A positive effect on cognition was suggested in 2 older studies of healthy elderly participants; however, meta-analysis could not be performed due to use of different preparations.(Szatmári 2008)
In a placebo-controlled, double-blind study, effects of Gerovital H3 on psychologic and physiologic functions were assessed in hospitalized older patients (mean age, 73). Patients received either a 5 mL injection or placebo intramuscularly 3 times per week for the first 6 weeks. The dose was doubled to 10 mL per injection during the second 6 weeks. Objective rating scales included interpersonal functioning, cognitive ability, psychiatric symptoms, and urine and blood chemical findings. Study results indicated that Gerovital H3 had no ameliorative effect on either psychologic or physiologic functioning.(Zwerling 1975)
Results have been conflicting but generally indicate that these compounds are ineffective in the treatment of any disease. In 1977, a comprehensive review of procaine use in more than 100,000 patients found no evidence of efficacy in treatment of the aging process or common age-related conditions.(Ostfeld 1977) Further reviews have found no scientific evidence to suggest an effect of procaine on aging.(Brodaty 1990, Perls 2013)
Depression
Procaine may act as a mild inhibitor of monoamine oxidase, thereby relieving depression.(Orgogozo 1987)
Nephritis
Animal data
Based on previous animal studies demonstrating dose-dependent inhibition of the RNA-binding protein Hu antigen R (HuR) and subsequent inflammatory gene transcriptions and reactions, researchers hypothesized that treatment with KH-3 would inhibit HuR-targeted inflammatory transcripts and inflammatory reactions, thereby improving glomerulosclerosis, in a rat model of nephritis, where glomerular HuR is activated and elevated. At a dose of 50 mg/kg/day for 5 days, intraperitoneal injection of KH-3 improved markers related to renal fibrosis, including serum urea levels, urinary protein excretion, glomerular matrix accumulation lesions, renal mRNA and key modulators of matrix accumulation, and fibrotic markers in the renal cortex. Additionally, KH-3 was a well-tolerated and safe treatment.(Liu 2020)
Dosing
There is no clinical evidence to support specific dosage recommendations for KH-3 or other procaine preparations.
Pregnancy / Lactation
Avoid use. Because of the lack of clinical trial data, procaine hydrochloride should not be used during pregnancy.
Interactions
KH-3 should not be coadministered with anticholinesterase agents (eg, neostigmine). Procaine may inhibit the bacteriostatic action of sulfonamides.(Brodaty 1990, McEvoy 2003)
KH-3 may antagonize the antibacterial effect of sulfonamides through para-aminobenzoic acid competition. Prolonged neuromuscular blockade may occur with concurrent use of KH-3 with succinylcholine. Coadministration with anticholinesterase and anticholinergic agents is a potential contraindication.(McEvoy 2003)
Adverse Reactions
Reports describe heartburn, restlessness, dizziness, migraine, and SLE following treatment with KH-3.(Brodaty 1990, Szatmári 2008)
Toxicology
No data.
References
Disclaimer
This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.
This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.
Further information
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